The liver has particular tolerogenic properties that allow its spontaneous acceptance in some animal species.Liver structure is considered to favor a tolerogenic environment.The peripheral tolerance mechanisms also pl...The liver has particular tolerogenic properties that allow its spontaneous acceptance in some animal species.Liver structure is considered to favor a tolerogenic environment.The peripheral tolerance mechanisms also play a role in spontaneous tolerance to liver graft.In a clinical setting,the main challenge nowadays facing liver transplantation is minimization of immunosuppression with the goal of donor-specific tolerance.Mechanisms involved in tolerance to transplanted organs are complex and partly unknown.A significant mechanism in tolerance induction is chimerism.Chimerism can be induced through transplantation of allogeneic donor bone marrow/stem cells under appropriate host conditioning.This review focuses on the tolerance mechanisms in liver transplantation and highlights the role of chimerism and allogeneic bone marrow/stem cell transplantation in tolerance development.展开更多
BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide.These defects generally result from severe trauma or resection of a whole large tumour.Autologous bone graft...BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide.These defects generally result from severe trauma or resection of a whole large tumour.Autologous bone grafts are the current gold standard for the reconstruction of such defects.However,due to increased patient morbidity and the need for a second operative site,other lines of treatment should be introduced.To find alternative unconventional therapies to manage such defects,bone tissue engineering using a combination of suitable bioactive factors,cells,and biocompatible scaffolds offers a promising new approach for bone regeneration.AIM To evaluate the healing capacity of platelet-rich fibrin(PRF)membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells(BMSCs)on critically sized mandibular defects in a rat model.METHODS Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine bur.Rats were allocated to three equal groups of 21 rats each.Group I bone defects were irrigated with normal saline and designed as negative controls.Defects of group II were grafted with PRF membranes and served as positive controls,while defects of group III were grafted with PRF membranes seeded with allogeneic BMSCs.Seven rats from each group were killed at 1,2 and 4 wk.The mandibles were dissected and prepared for routine haematoxylin and eosin(HE)staining,Masson's trichrome staining and CD68 immunohistochemical staining.RESULTS Four weeks postoperatively,the percentage area of newly formed bone was significantly higher in group III(0.88±0.02)than in groups I(0.02±0.00)and II(0.60±0.02).The amount of granulation tissue formation was lower in group III(0.12±0.02)than in groups I(0.20±0.02)and II(0.40±0.02).The number of inflammatory cells was lower in group III(0.29±0.03)than in groups I(4.82±0.08)and II(3.09±0.07).CONCLUSION Bone regenerative quality of critically sized mandibular bone defects in rats was better promoted by PRF membranes seeded with BMSCs than with PRF membranes alone.展开更多
Objective To explore the effect of α-galactosyleramide (α-GalCer) on immune reconstitu-tion under acute graft-versus-host disease (aGVHD). Methods BALB/c mice were transplanted with allogeneic C57BL/6 bone marrow ce...Objective To explore the effect of α-galactosyleramide (α-GalCer) on immune reconstitu-tion under acute graft-versus-host disease (aGVHD). Methods BALB/c mice were transplanted with allogeneic C57BL/6 bone marrow cells and splenocytes (both 1×107) after receiving lethal total-body irradiation. α-GalCer (100 ug/kg) or vehicle (dimethylsulfoxide) was administered intraperitoneally immediately after transplantation. The effects of α-GalCer on immune reconstitution, proliferation of T cells and B cells, hemato-poiesis, and thymic microenvironment were assessed. Results The α-GalCer group exhibited higher percentages of CD3+, CD4+, CD8+, B220+, CD40+, and CD86+ cells compared with the vehicle group. The number of colony forming unit per 1000 CD34+ cells in the α-GalCer group was higher than in the vehicle group (P=0.0012). In vitro proliferation assays showed that the α-GalCer group had higher percentages of CD3+, CD4+, CD8+, and B220+ cells compared with the vehicle group. As for the results of in vivo prolifera-tion assays, the numbers of CD3+, CD4+, CD8+, and B220+ cells were higher in the α-GalCer group than in the normal group, especially the number of B220+ cells (P=0.007). Significant difference was not found in thymocyte count between the α-GalCer group and the vehicle group, nor in the percentages of CD3+, CD4+, and CD8+ cells. Conclusion Administration of α-GalCer after allogeneic bone marrow transplantation may promote immune reconstitution in the presence of aGVHD.展开更多
In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause e...In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition;in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer’s disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin, on bone and osteometabolic diseases. However, statins in high doses cause inflammation in bone defects and inhibit osteoblastic differentiation, negatively contributing to bone repair. Thus, different types of studies with different concentrations of statins have been studied to positively or negatively correlate this drug with bone regeneration. In this review we will address the positive, negative or neutral effects of statins in relation to bone defects providing a comprehensive understanding of their application. Finally, we will discuss a variety of statin-based drugs and the ideal dose through a theoretical basis with preclinical, clinical and laboratory work in order to promote the repair of bone defects.展开更多
1. Introduction The tegmental wall of the tympanic cavity is a thin plate of the temporal bone that separates the middle cranial fossa(MCF) from the ear. This anatomical region consists of two areas: an anterior one, ...1. Introduction The tegmental wall of the tympanic cavity is a thin plate of the temporal bone that separates the middle cranial fossa(MCF) from the ear. This anatomical region consists of two areas: an anterior one, comprised of the tegmen tympani(To′th et al., 2007), and a posterior one, formed by the tegmen antri and the tegmen mastoideum(Makki et al., 2011). In some patients, the tegmental region of the temporal bone can be interrupted, causing a tegmen defect(TD). A TD is sometimes associated with a meningoencephalic herniation(MEH), in which brain tissue herniates through a TD.展开更多
Introduction: Prostate cancer is the most frequently diagnosed male malignancy and the fifth leading cause of cancer death in men worldwide. Since the advent of screening methods such as Prostate Specific Antigen (PSA...Introduction: Prostate cancer is the most frequently diagnosed male malignancy and the fifth leading cause of cancer death in men worldwide. Since the advent of screening methods such as Prostate Specific Antigen (PSA) assay, digital rectal examination (DRE) and prostate biopsy, its incidence has increased significantly. The aim of our study was to analyse aspects of bone scintigraphy (BS) as part of the metastatic extension assessment of prostate cancer in Senegal. Patients and Methods: This was a retrospective descriptive and analytical study, running from January 1<sup>er</sup> 2022 to August 31 2023. Patients with histologically confirmed prostate cancer were included. Whole-body scans (WBS) were performed using a dual-head SPECT gamma camera (Mediso Nucline TM Spirit DH-V type), 3 hours after intravenous injection of 8 MBq/kg (555 to 740 MBq) of <sup>99m</sup>Tc-HMDP. Results: A total of 288 patients with a mean age of 68.37 ± 7.79 years were included. The median total PSA level was 97.6 ng/ml, with 144 patients having a level greater than or equal to 20 ng/ml. All patients had adenocarcinoma, and the Gleason score was available in 202 (70.13%) patients, 75.75% of whom had a score greater than or equal to 7. BS was contributory in 70.48% of cases, with 30.90% positive and 39.58% negative. The result was inconclusive in 85 patients (29.51%). The mean PSA for patients with a positive scan was 190.2 ng/ml and 40.6 ng/ml for those with a negative scan. Multiple metastatic lesions predominated (87.35% of cases). Metastatic lesions occurred preferentially in the axial skeleton, with a proportion of 68% versus 32% in the appendicular skeleton. Classification of bone metastases according to the SOLOWAY score revealed grade I (62.07%), grade II (35.63%) and grade IV (2.30%). Conclusion: In Senegal, prostate cancer is generally diagnosed in men of advanced age. The presence of bone metastases is frequent in its evolution, transforming a curable localized disease into a generalized disease with a compromised prognosis. Bone scintigraphy remains an essential part of the initial work-up and evaluation of response to treatment.展开更多
Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed th...Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.展开更多
BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To e...BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.展开更多
Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been ...Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been used to avoid the morbidity and insufficient quantity associated with harvesting autologous bone. The primary objective of this retrospective study was to determine whether, in patients with increased risk of operative nonunion related to multilevel fusion, adding DBM fibers to mineralized bone allograft resulted in better fusion than using allograft alone. The secondary objectives were to evaluate how adding DBM fibers affects functional disability, low back pain, intraoperative blood loss and the nonunion rate. Methods: This retrospective study involved a chart review of consecutive patients who underwent multilevel lumbar spinal fusion and were operated on by a single surgeon. The patients were divided into two groups: 14 patients received mineralized bone allograft (control group) and 14 patients received a combination of mineralized bone allograft and DBM (experimental group). Patients were reviewed at a mean of 16.4 ± 2.2 months after surgery at which point CT scans were analyzed to determine whether fusion had occurred;Oswestry disability index (ODI) and pain were also evaluated. Results: A mean of 5 levels [min 2, max 13] were fused in these patients. Posterolateral fusion as defined by the Lenke classification was not significantly different between groups. The experimental DBM group had a significantly better composite fusion score than the control group (P Discussion: Adding DBM fibers to allograft bone during multilevel posterolateral spinal fusion was safe and produced better composite fusion than using allograft only as an autograft extender.展开更多
It is important for surgeons performing sarcoma surgery to know that bone resection and tumor prosthesis applications in soft tissue sarcomas(STS)have unique features in terms of indication,surgical approach and follo...It is important for surgeons performing sarcoma surgery to know that bone resection and tumor prosthesis applications in soft tissue sarcomas(STS)have unique features in terms of indication,surgical approach and follow-up,in terms of the management of these cases.Some STS are associated with bone and major neurovascular structures.Bone-associated STS are generally relatively large and relatively deep-seated.Additionally,the tendency for metastasis is high.In some cases,the decision about which structures to resect is difficult.These cases are often accompanied by poor oncological and surgical outcomes.Management of cases should be done by a multidisciplinary team in advanced centers specialized in this field.The surgical team must have sufficient knowledge and experience in the field of limb-sparing surgery.Preoperative evaluation and especially good planning of bone and soft tissue reconstruction are vital.展开更多
Introduction: Pseudarthrosis (PSA) of the diaphysis of long bones still remains a current problem, despite improvements in the treatment of these fractures. Our study aims to study the epidemiological and therapeutic ...Introduction: Pseudarthrosis (PSA) of the diaphysis of long bones still remains a current problem, despite improvements in the treatment of these fractures. Our study aims to study the epidemiological and therapeutic aspects of PSA of the diaphysis of long bones. Method: This retrospective work concerns 30 cases of non-union of the diaphysis of long bones treated in the orthopedic and trauma surgery department at Donka National Hospital, during a period of 18 months from January 1, 2019 to June 30, 2020. Results: We recruited 30 patients, 80% of whom were male, with an average age of 39.9 years. Public road accidents (AVP) represented the main cause of fractures of the diaphysis of long bones 87%, they were open in 25 cases or 83%. The fractures were located in the middle 1/3 of the diaphysis of the long bones in 50% of cases. Treatment of initial fractures was traditional in 21 cases, orthopedic in 2 cases and surgical in 7 cases. It was aseptic nonunion in 28 cases (93%) and septic nonunion in 2 cases. They were hypertrophic in 7 cases, slightly hypertrophic in 5 cases, oligotrophic in 11 cases, atrophic in 6 cases and with bone defect in 1 case. The treatment was based on osteosynthesis including 16 cases of screwed “PV” plate: 7 cases of centromedullary “ECM” nailing, 2 cases of external fixator, 1 case of broaching and 4 cases of Plastering. The results according to ASAMI criteria on an anatomical level were excellent in 19 cases, good in 3 cases and poor in 3 cases, with a union rate of 76%. And 5 patients undergoing consolidation. Conclusion: Based on the literature data and the experience of our department, the true treatment of PSA requires correct management of the initial fracture without forgetting the interest in preventing AVP which appears to be an element essential, making it possible to reduce the incidence of fractures of the diaphysis.展开更多
Background: When applied to trabecular bone X-ray images, the anisotropic properties of trabeculae located at ultra-distal radius were investigated by using the trabecular bone scores (TBS) calculated along directions...Background: When applied to trabecular bone X-ray images, the anisotropic properties of trabeculae located at ultra-distal radius were investigated by using the trabecular bone scores (TBS) calculated along directions parallel and perpendicular to the forearm. Methodology: Data from more than two hundred subjects were studied retrospectively. A DXA (GE Lunar Prodigy) scan of the forearm was performed on each subject to measure the bone mineral density (BMD) value at the location of ultra-distal radius, and an X-ray digital image of the same forearm was taken on the same day. The values of trabecular bone score along the direction perpendicular to the forearm, TBS<sub>x</sub>, and along the direction parallel to the forearm, TBS<sub>y</sub>, were calculated respectively. The statistics of TBS<sub>x</sub> and TBS<sub>y</sub> were calculated, and the anisotropy of the trabecular bone, which was defined as the ratio of TBS<sub>y</sub> to TBS<sub>x</sub> and changed with subjects’ BMD and age, was reported and analyzed. Results: The results show that the correlation coefficient between TBS<sub>x</sub> and TBS<sub>y</sub> was 0.72 (p BMD and age was reported. The results showed that decreased trabecular bone anisotropy was associated with deceased BMD and increased age in the subject group. Conclusions: This study shows that decreased trabecular bone anisotropy was associated with decreased BMD and increased age.展开更多
Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human...Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor tissueregeneration.Thus,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic lineage.In this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based deposition.The inclusion of the nanofiller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon printing.The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)model.The inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven days.This study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.展开更多
Background The effect of microbial phytase on amino acid and energy digestibility is not consistent in pigs,which may be related to the phytase dosage or the adaptation length to the diet.Therefore,an experiment was c...Background The effect of microbial phytase on amino acid and energy digestibility is not consistent in pigs,which may be related to the phytase dosage or the adaptation length to the diet.Therefore,an experiment was conducted to test the hypotheses that increasing dietary phytase after an 18-day adaptation period:1)increases nutrient and energy digestibility;2)increases plasma P,plasma inositol,and bone ash of young pigs;and 3)demonstrates that maximum phytate degradation requires more phytase than maximum P digestibility.Results Data indicated that increasing inclusion of phytase[0,250,500,1,000,2,000,and 4,000 phytase units(FTU)/kg feed]in corn-soybean meal-based diets increased apparent ileal digestibility(AID)of Trp(quadratic;P<0.05),and of Lys and Thr(linear;P<0.05),and tended to increase AID of Met(linear;P<0.10).Increasing dietary phytase also increased AID and apparent total tract digestibility(ATTD)of Ca and P(quadratic;P<0.05)and increased ATTD of K and Na(linear;P<0.05),but phytase did not influence the ATTD of Mg or gross energy.Concentrations of plasma P and bone ash increased(quadratic;P<0.05),and plasma inositol also increased(linear;P<0.05)with increasing inclusion of phytase.Reduced concentrations of inositol phosphate(IP)6 and IP5(quadratic;P<0.05),reduced IP4 and IP3(linear;P<0.05),but increased inositol concentrations(linear;P<0.05)were observed in ileal digesta as dietary phytase increased.The ATTD of P was maximized if at least 1,200 FTU/kg were used,whereas more than 4,000 FTU/kg were needed to maximize inositol release.Conclusions Increasing dietary levels of phytase after an 18-day adaptation period increased phytate and IP ester degradation and inositol release in the small intestine.Consequently,increasing dietary phytase resulted in improved digestibility of Ca,P,K,Na,and the first 4 limiting amino acids,and in increased concentrations of bone ash and plasma P and inositol.In a corn-soybean meal diet,maximum inositol release requires approximately 3,200 FTU/kg more phytase than that required for maximum P digestibility.展开更多
Bone collagen hydrolysates(peptides)derived from byproduct of animal product processing have been used to produce commercially valuable products due to their potential antioxidant activity.Maillard glycosylated reacti...Bone collagen hydrolysates(peptides)derived from byproduct of animal product processing have been used to produce commercially valuable products due to their potential antioxidant activity.Maillard glycosylated reaction is considered as a promising method to enhance the antioxidant activity of peptides.Hence,this research aims at investigating the Maillard glycosylation activity and antioxidant activity of bone collagen hydrolysates from different sources.In this study,3 glycosylated bone collagen hydrolysates were prepared and characterized,and cytotoxicity and antioxidant activity were analyzed and evaluated.The free amino groups loss,browning intensity,and fluorescence intensity of G-Cbcp(glycosylated chicken bone collagen hydrolysates(peptides))were the heaviest,followed by G-Pbcp(glycosylated porcine bone collagen hydrolysates(peptides))and G-Bbcp(glycosylated bovine bone collagen hydrolysates(peptides)).The results of amino acid analysis showed that amino acid composition of different bone collagen hydrolysates was significantly different and the amino acid decreased to different degrees after Maillard glycosylated reaction,which may lead to differences in Maillard glycosylated reaction activity.Furthermore,the 3 glycosylated hydrolysates showed no significant cytotoxicity.The results showed that glycosylation process significantly increased the antioxidant activity of bone collagen hydrolysates,and G-Cbcp showed the strongest antioxidant activity,followed by G-Pbcp and G-Bbcp.Therefore,compared with the bone collagen hydrolysates,3 glycosylated hydrolysates showed significant characteristic and structural changes,and higher antioxidant activity.展开更多
In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we dev...In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.展开更多
BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or to...BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.展开更多
BACKGROUND Osteoporosis(OP)has become a major public health problem worldwide.Most OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing ...BACKGROUND Osteoporosis(OP)has become a major public health problem worldwide.Most OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing osteogenesis.In the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic environment.Recently,a few studies have demonstrated that hypoxiainducible factor 2alpha(HIF-2α)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been determined.AIM To investigate the effect of HIF-2αon the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of OP.METHODS Mice with BMSC-specific HIF-2αknockout(Prx1-Cre;Hif-2αfl/fl mice)were used for in vivo experiments.Bone quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone treatment.Moreover,the hematopoietic function of HSCs in the BM niche was compared between the two mouse genotypes.In vitro,the HIF-2αagonist roxadustat and the HIF-2αinhibitor PT2399 were used to investigate the function of HIF-2αin BMSC osteogenic and adipogenic differentiation.Finally,we investigated the effect of HIF-2αon BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY1485 and the mTOR inhibitor rapamycin.RESULTS The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2αfl/fl mice was lower than that of Hif-2αfl/fl mice under the three intervention conditions.In vitro,Hif-2αfl/fl mouse BMSCs were cultured and treated with the HIF-2αagonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14 d of osteogenic differentiation,BMSCs treated with roxadustat exhibited increased expression of osteogenesis-related genes.The opposite effects were shown for mouse BMSCs treated with the HIF-2αinhibitor PT2399.The mTOR inhibitor rapamycin was used to confirm that HIF-2αregulated BMSC osteogenic and adipogenic differentiation by inhibiting the mTOR pathway.Consequently,there was no significant difference in the hematopoietic function of HSCs between Prx1-Cre;Hif-2αfl/fl and Hif-2αfl/fl mice.CONCLUSION Our study showed that inhibition of HIF-2αdecreases bone mass by inhibiting the osteogenic differentiation and increasing the adipogenic differentiation of BMSCs through inhibition of mTOR signaling in the BM niche.展开更多
Background: Renal osteodystrophy (ROD) is a bone disorder resulting from chronic kidney disease (CKD) and related metabolic diseases. Dickkopf-related protein-1 (DKK-1) is critical in regulating bone biology. This stu...Background: Renal osteodystrophy (ROD) is a bone disorder resulting from chronic kidney disease (CKD) and related metabolic diseases. Dickkopf-related protein-1 (DKK-1) is critical in regulating bone biology. This study aimed to evaluate the serum DKK-1 level as a bone marker in children with CKD who undergo regular hemodialysis (HD). Subjects and Methods: This case-control study involved 40 children with CKD on HD and 40 healthy children as controls. The study measured serum DKK-1 levels and performed a dual-energy X-ray absorptiometry scan (DEXA) in line with routine laboratory investigations. Results: There was a significant increase in the serum level of DKK-1 in the patient group compared to the control group. The DKK-1 levels were 2540.65 (2215.4 - 2909.2) pg/ml and 1110.45 (885.45 - 1527.65) pg/ml, respectively, with a p-value of less than 0.001. In the hemodialysis group, 25 patients (62.5%) had low bone mineral density (BMD) with a Z-score of under -2.0. Eighteen of these patients had low BMD in both the neck of the femur and lumbar spines. Additionally, there was a significant increase in serum DKK-1 level in patients with low BMD (2567.35 (2303.8 - 3108.1) pg/ml) compared to patients with normal BMD (2454 (1859 - 2820) pg/ml) (p = 0.041). There was also a significant positive correlation between DKK1 level and phosphorus, alkaline phosphatase, and Parathormone serum levels. In conclusion, the study indicates a clear correlation between DKK-1 and BMD in children undergoing maintenance hemodialysis. DKK1 is a promising biomarker for CKD-MBD.展开更多
文摘The liver has particular tolerogenic properties that allow its spontaneous acceptance in some animal species.Liver structure is considered to favor a tolerogenic environment.The peripheral tolerance mechanisms also play a role in spontaneous tolerance to liver graft.In a clinical setting,the main challenge nowadays facing liver transplantation is minimization of immunosuppression with the goal of donor-specific tolerance.Mechanisms involved in tolerance to transplanted organs are complex and partly unknown.A significant mechanism in tolerance induction is chimerism.Chimerism can be induced through transplantation of allogeneic donor bone marrow/stem cells under appropriate host conditioning.This review focuses on the tolerance mechanisms in liver transplantation and highlights the role of chimerism and allogeneic bone marrow/stem cell transplantation in tolerance development.
文摘BACKGROUND Critically sized bone defects represent a significant challenge to orthopaedic surgeons worldwide.These defects generally result from severe trauma or resection of a whole large tumour.Autologous bone grafts are the current gold standard for the reconstruction of such defects.However,due to increased patient morbidity and the need for a second operative site,other lines of treatment should be introduced.To find alternative unconventional therapies to manage such defects,bone tissue engineering using a combination of suitable bioactive factors,cells,and biocompatible scaffolds offers a promising new approach for bone regeneration.AIM To evaluate the healing capacity of platelet-rich fibrin(PRF)membranes seeded with allogeneic mesenchymal bone marrow-derived stem cells(BMSCs)on critically sized mandibular defects in a rat model.METHODS Sixty-three Sprague Dawley rats were subjected to bilateral bone defects of critical size in the mandibles created by a 5-mm diameter trephine bur.Rats were allocated to three equal groups of 21 rats each.Group I bone defects were irrigated with normal saline and designed as negative controls.Defects of group II were grafted with PRF membranes and served as positive controls,while defects of group III were grafted with PRF membranes seeded with allogeneic BMSCs.Seven rats from each group were killed at 1,2 and 4 wk.The mandibles were dissected and prepared for routine haematoxylin and eosin(HE)staining,Masson's trichrome staining and CD68 immunohistochemical staining.RESULTS Four weeks postoperatively,the percentage area of newly formed bone was significantly higher in group III(0.88±0.02)than in groups I(0.02±0.00)and II(0.60±0.02).The amount of granulation tissue formation was lower in group III(0.12±0.02)than in groups I(0.20±0.02)and II(0.40±0.02).The number of inflammatory cells was lower in group III(0.29±0.03)than in groups I(4.82±0.08)and II(3.09±0.07).CONCLUSION Bone regenerative quality of critically sized mandibular bone defects in rats was better promoted by PRF membranes seeded with BMSCs than with PRF membranes alone.
基金Supported by National Natural Science Foundation of China (30670898, 30572108)National Basic Research Program of China (973 Program) (2005CB522400)Capital Research Fund for Medical Development (2007-2040)
文摘Objective To explore the effect of α-galactosyleramide (α-GalCer) on immune reconstitu-tion under acute graft-versus-host disease (aGVHD). Methods BALB/c mice were transplanted with allogeneic C57BL/6 bone marrow cells and splenocytes (both 1×107) after receiving lethal total-body irradiation. α-GalCer (100 ug/kg) or vehicle (dimethylsulfoxide) was administered intraperitoneally immediately after transplantation. The effects of α-GalCer on immune reconstitution, proliferation of T cells and B cells, hemato-poiesis, and thymic microenvironment were assessed. Results The α-GalCer group exhibited higher percentages of CD3+, CD4+, CD8+, B220+, CD40+, and CD86+ cells compared with the vehicle group. The number of colony forming unit per 1000 CD34+ cells in the α-GalCer group was higher than in the vehicle group (P=0.0012). In vitro proliferation assays showed that the α-GalCer group had higher percentages of CD3+, CD4+, CD8+, and B220+ cells compared with the vehicle group. As for the results of in vivo prolifera-tion assays, the numbers of CD3+, CD4+, CD8+, and B220+ cells were higher in the α-GalCer group than in the normal group, especially the number of B220+ cells (P=0.007). Significant difference was not found in thymocyte count between the α-GalCer group and the vehicle group, nor in the percentages of CD3+, CD4+, and CD8+ cells. Conclusion Administration of α-GalCer after allogeneic bone marrow transplantation may promote immune reconstitution in the presence of aGVHD.
文摘In the medical and dental field, the importance and need for the study of materials and drugs for use as bone grafts or regeneration in injured areas due to the presence of fractures, infections or tumors that cause extensive loss of bone tissue is observed. Bone is a specialized, vascularized and dynamic connective tissue that changes throughout the life of the organism. When injured, it has a unique ability to regenerate and repair without the presence of scars, but in some situations, due to the size of the defect, the bone tissue does not regenerate completely. Thus, due to its importance, there is a great development in therapeutic approaches for the treatment of bone defects through studies that include autografts, allografts and artificial materials used alone or in association with bone grafts. Pharmaceuticals composed of biomaterials and osteogenic active substances have been extensively studied because they provide potential for tissue regeneration and new strategies for the treatment of bone defects. Statins work as specific inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoAreductase). They represent efficient drugs in lowering cholesterol, as they reduce platelet aggregation and thrombus deposition;in addition, they promote angiogenesis, reduce the β-amyloid peptide related to Alzheimer’s disease and suppress the activation of T lymphocytes. Furthermore, these substances have been used in the treatment of hypercholesterolemia and coronary artery disease. By inhibiting HMG-CoAreductase, statins not only inhibit cholesterol synthesis, but also exhibit several other beneficial pleiotropic effects. Therefore, there has been increasing interest in researching the effects of statins, including Simvastatin, on bone and osteometabolic diseases. However, statins in high doses cause inflammation in bone defects and inhibit osteoblastic differentiation, negatively contributing to bone repair. Thus, different types of studies with different concentrations of statins have been studied to positively or negatively correlate this drug with bone regeneration. In this review we will address the positive, negative or neutral effects of statins in relation to bone defects providing a comprehensive understanding of their application. Finally, we will discuss a variety of statin-based drugs and the ideal dose through a theoretical basis with preclinical, clinical and laboratory work in order to promote the repair of bone defects.
文摘1. Introduction The tegmental wall of the tympanic cavity is a thin plate of the temporal bone that separates the middle cranial fossa(MCF) from the ear. This anatomical region consists of two areas: an anterior one, comprised of the tegmen tympani(To′th et al., 2007), and a posterior one, formed by the tegmen antri and the tegmen mastoideum(Makki et al., 2011). In some patients, the tegmental region of the temporal bone can be interrupted, causing a tegmen defect(TD). A TD is sometimes associated with a meningoencephalic herniation(MEH), in which brain tissue herniates through a TD.
文摘Introduction: Prostate cancer is the most frequently diagnosed male malignancy and the fifth leading cause of cancer death in men worldwide. Since the advent of screening methods such as Prostate Specific Antigen (PSA) assay, digital rectal examination (DRE) and prostate biopsy, its incidence has increased significantly. The aim of our study was to analyse aspects of bone scintigraphy (BS) as part of the metastatic extension assessment of prostate cancer in Senegal. Patients and Methods: This was a retrospective descriptive and analytical study, running from January 1<sup>er</sup> 2022 to August 31 2023. Patients with histologically confirmed prostate cancer were included. Whole-body scans (WBS) were performed using a dual-head SPECT gamma camera (Mediso Nucline TM Spirit DH-V type), 3 hours after intravenous injection of 8 MBq/kg (555 to 740 MBq) of <sup>99m</sup>Tc-HMDP. Results: A total of 288 patients with a mean age of 68.37 ± 7.79 years were included. The median total PSA level was 97.6 ng/ml, with 144 patients having a level greater than or equal to 20 ng/ml. All patients had adenocarcinoma, and the Gleason score was available in 202 (70.13%) patients, 75.75% of whom had a score greater than or equal to 7. BS was contributory in 70.48% of cases, with 30.90% positive and 39.58% negative. The result was inconclusive in 85 patients (29.51%). The mean PSA for patients with a positive scan was 190.2 ng/ml and 40.6 ng/ml for those with a negative scan. Multiple metastatic lesions predominated (87.35% of cases). Metastatic lesions occurred preferentially in the axial skeleton, with a proportion of 68% versus 32% in the appendicular skeleton. Classification of bone metastases according to the SOLOWAY score revealed grade I (62.07%), grade II (35.63%) and grade IV (2.30%). Conclusion: In Senegal, prostate cancer is generally diagnosed in men of advanced age. The presence of bone metastases is frequent in its evolution, transforming a curable localized disease into a generalized disease with a compromised prognosis. Bone scintigraphy remains an essential part of the initial work-up and evaluation of response to treatment.
基金Indian Council of Medical Research,2020-0282/SCR/ADHOC-BMSDepartment of Science and Technology,India,DST/INSPIRE Fellowship:2021/IF210073.
文摘Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.
基金Supported by the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation,No.GZC20231088President Foundation of The Third Affiliated Hospital of Southern Medical University,China,No.YP202210.
文摘BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.
文摘Introduction: While autograft bone is the gold standard for multilevel posterolateral lumbar fusion, bone substitutes and graft extenders such as allograft bone, ceramics and demineralized bone matrix (DBM) have been used to avoid the morbidity and insufficient quantity associated with harvesting autologous bone. The primary objective of this retrospective study was to determine whether, in patients with increased risk of operative nonunion related to multilevel fusion, adding DBM fibers to mineralized bone allograft resulted in better fusion than using allograft alone. The secondary objectives were to evaluate how adding DBM fibers affects functional disability, low back pain, intraoperative blood loss and the nonunion rate. Methods: This retrospective study involved a chart review of consecutive patients who underwent multilevel lumbar spinal fusion and were operated on by a single surgeon. The patients were divided into two groups: 14 patients received mineralized bone allograft (control group) and 14 patients received a combination of mineralized bone allograft and DBM (experimental group). Patients were reviewed at a mean of 16.4 ± 2.2 months after surgery at which point CT scans were analyzed to determine whether fusion had occurred;Oswestry disability index (ODI) and pain were also evaluated. Results: A mean of 5 levels [min 2, max 13] were fused in these patients. Posterolateral fusion as defined by the Lenke classification was not significantly different between groups. The experimental DBM group had a significantly better composite fusion score than the control group (P Discussion: Adding DBM fibers to allograft bone during multilevel posterolateral spinal fusion was safe and produced better composite fusion than using allograft only as an autograft extender.
文摘It is important for surgeons performing sarcoma surgery to know that bone resection and tumor prosthesis applications in soft tissue sarcomas(STS)have unique features in terms of indication,surgical approach and follow-up,in terms of the management of these cases.Some STS are associated with bone and major neurovascular structures.Bone-associated STS are generally relatively large and relatively deep-seated.Additionally,the tendency for metastasis is high.In some cases,the decision about which structures to resect is difficult.These cases are often accompanied by poor oncological and surgical outcomes.Management of cases should be done by a multidisciplinary team in advanced centers specialized in this field.The surgical team must have sufficient knowledge and experience in the field of limb-sparing surgery.Preoperative evaluation and especially good planning of bone and soft tissue reconstruction are vital.
文摘Introduction: Pseudarthrosis (PSA) of the diaphysis of long bones still remains a current problem, despite improvements in the treatment of these fractures. Our study aims to study the epidemiological and therapeutic aspects of PSA of the diaphysis of long bones. Method: This retrospective work concerns 30 cases of non-union of the diaphysis of long bones treated in the orthopedic and trauma surgery department at Donka National Hospital, during a period of 18 months from January 1, 2019 to June 30, 2020. Results: We recruited 30 patients, 80% of whom were male, with an average age of 39.9 years. Public road accidents (AVP) represented the main cause of fractures of the diaphysis of long bones 87%, they were open in 25 cases or 83%. The fractures were located in the middle 1/3 of the diaphysis of the long bones in 50% of cases. Treatment of initial fractures was traditional in 21 cases, orthopedic in 2 cases and surgical in 7 cases. It was aseptic nonunion in 28 cases (93%) and septic nonunion in 2 cases. They were hypertrophic in 7 cases, slightly hypertrophic in 5 cases, oligotrophic in 11 cases, atrophic in 6 cases and with bone defect in 1 case. The treatment was based on osteosynthesis including 16 cases of screwed “PV” plate: 7 cases of centromedullary “ECM” nailing, 2 cases of external fixator, 1 case of broaching and 4 cases of Plastering. The results according to ASAMI criteria on an anatomical level were excellent in 19 cases, good in 3 cases and poor in 3 cases, with a union rate of 76%. And 5 patients undergoing consolidation. Conclusion: Based on the literature data and the experience of our department, the true treatment of PSA requires correct management of the initial fracture without forgetting the interest in preventing AVP which appears to be an element essential, making it possible to reduce the incidence of fractures of the diaphysis.
文摘Background: When applied to trabecular bone X-ray images, the anisotropic properties of trabeculae located at ultra-distal radius were investigated by using the trabecular bone scores (TBS) calculated along directions parallel and perpendicular to the forearm. Methodology: Data from more than two hundred subjects were studied retrospectively. A DXA (GE Lunar Prodigy) scan of the forearm was performed on each subject to measure the bone mineral density (BMD) value at the location of ultra-distal radius, and an X-ray digital image of the same forearm was taken on the same day. The values of trabecular bone score along the direction perpendicular to the forearm, TBS<sub>x</sub>, and along the direction parallel to the forearm, TBS<sub>y</sub>, were calculated respectively. The statistics of TBS<sub>x</sub> and TBS<sub>y</sub> were calculated, and the anisotropy of the trabecular bone, which was defined as the ratio of TBS<sub>y</sub> to TBS<sub>x</sub> and changed with subjects’ BMD and age, was reported and analyzed. Results: The results show that the correlation coefficient between TBS<sub>x</sub> and TBS<sub>y</sub> was 0.72 (p BMD and age was reported. The results showed that decreased trabecular bone anisotropy was associated with deceased BMD and increased age in the subject group. Conclusions: This study shows that decreased trabecular bone anisotropy was associated with decreased BMD and increased age.
基金supported by grants from the Biotechnology and Biological Sciences Research Council(Nos.BBSRC LO21071/and BB/L00609X/1)UK Regenerative Medicine Platform Hub Acellular Approaches for Therapeutic Delivery(No.MR/K026682/1)+3 种基金Acellular Hub,SMART Materials 3D Architecture(No.MR/R015651/1)the UK Regenerative Medicine Platform(No.MR/L012626/1 Southampton Imaging)to ROCOMRCAMED Regenerative Medicine and Stem Cell Research Initiative(No.MR/V00543X/1)to JID,ROCO and YHKGC acknowledges funding from AIRC Aldi Fellowship under grant agreement No.25412.
文摘Autograft or metal implants are routinely used in skeletal repair.However,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering alternative.The use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor tissueregeneration.Thus,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic lineage.In this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based deposition.The inclusion of the nanofiller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon printing.The composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)model.The inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven days.This study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.
基金support for this research from AB Vista,Marlborough,UK,is greatly appreciated。
文摘Background The effect of microbial phytase on amino acid and energy digestibility is not consistent in pigs,which may be related to the phytase dosage or the adaptation length to the diet.Therefore,an experiment was conducted to test the hypotheses that increasing dietary phytase after an 18-day adaptation period:1)increases nutrient and energy digestibility;2)increases plasma P,plasma inositol,and bone ash of young pigs;and 3)demonstrates that maximum phytate degradation requires more phytase than maximum P digestibility.Results Data indicated that increasing inclusion of phytase[0,250,500,1,000,2,000,and 4,000 phytase units(FTU)/kg feed]in corn-soybean meal-based diets increased apparent ileal digestibility(AID)of Trp(quadratic;P<0.05),and of Lys and Thr(linear;P<0.05),and tended to increase AID of Met(linear;P<0.10).Increasing dietary phytase also increased AID and apparent total tract digestibility(ATTD)of Ca and P(quadratic;P<0.05)and increased ATTD of K and Na(linear;P<0.05),but phytase did not influence the ATTD of Mg or gross energy.Concentrations of plasma P and bone ash increased(quadratic;P<0.05),and plasma inositol also increased(linear;P<0.05)with increasing inclusion of phytase.Reduced concentrations of inositol phosphate(IP)6 and IP5(quadratic;P<0.05),reduced IP4 and IP3(linear;P<0.05),but increased inositol concentrations(linear;P<0.05)were observed in ileal digesta as dietary phytase increased.The ATTD of P was maximized if at least 1,200 FTU/kg were used,whereas more than 4,000 FTU/kg were needed to maximize inositol release.Conclusions Increasing dietary levels of phytase after an 18-day adaptation period increased phytate and IP ester degradation and inositol release in the small intestine.Consequently,increasing dietary phytase resulted in improved digestibility of Ca,P,K,Na,and the first 4 limiting amino acids,and in increased concentrations of bone ash and plasma P and inositol.In a corn-soybean meal diet,maximum inositol release requires approximately 3,200 FTU/kg more phytase than that required for maximum P digestibility.
基金supported by the National Natural Science Foundation of China(32101883)Fellowship China Postdoctoral Science Foundation(2021M693902)National Agricultural Science and Technology Innovation Project(CAAS-ASTIP-2022)。
文摘Bone collagen hydrolysates(peptides)derived from byproduct of animal product processing have been used to produce commercially valuable products due to their potential antioxidant activity.Maillard glycosylated reaction is considered as a promising method to enhance the antioxidant activity of peptides.Hence,this research aims at investigating the Maillard glycosylation activity and antioxidant activity of bone collagen hydrolysates from different sources.In this study,3 glycosylated bone collagen hydrolysates were prepared and characterized,and cytotoxicity and antioxidant activity were analyzed and evaluated.The free amino groups loss,browning intensity,and fluorescence intensity of G-Cbcp(glycosylated chicken bone collagen hydrolysates(peptides))were the heaviest,followed by G-Pbcp(glycosylated porcine bone collagen hydrolysates(peptides))and G-Bbcp(glycosylated bovine bone collagen hydrolysates(peptides)).The results of amino acid analysis showed that amino acid composition of different bone collagen hydrolysates was significantly different and the amino acid decreased to different degrees after Maillard glycosylated reaction,which may lead to differences in Maillard glycosylated reaction activity.Furthermore,the 3 glycosylated hydrolysates showed no significant cytotoxicity.The results showed that glycosylation process significantly increased the antioxidant activity of bone collagen hydrolysates,and G-Cbcp showed the strongest antioxidant activity,followed by G-Pbcp and G-Bbcp.Therefore,compared with the bone collagen hydrolysates,3 glycosylated hydrolysates showed significant characteristic and structural changes,and higher antioxidant activity.
基金supported by the National Key R&D Program of China[grant number 2021YFC2400700]the National Natural Science Foundation of China[grant numbers 82170929,81970908 and 81771039].
文摘In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.
基金Supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2022YFA1105800the National Natural Science Foundation of China,No.81970940.
文摘BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.
基金Supported by Basic and Applied Basic Research Foundation of Guangdong Province,No.2020A1515010123 and No.2021A1515010695Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province,No.2019A030317011.
文摘BACKGROUND Osteoporosis(OP)has become a major public health problem worldwide.Most OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing osteogenesis.In the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic environment.Recently,a few studies have demonstrated that hypoxiainducible factor 2alpha(HIF-2α)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been determined.AIM To investigate the effect of HIF-2αon the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of OP.METHODS Mice with BMSC-specific HIF-2αknockout(Prx1-Cre;Hif-2αfl/fl mice)were used for in vivo experiments.Bone quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone treatment.Moreover,the hematopoietic function of HSCs in the BM niche was compared between the two mouse genotypes.In vitro,the HIF-2αagonist roxadustat and the HIF-2αinhibitor PT2399 were used to investigate the function of HIF-2αin BMSC osteogenic and adipogenic differentiation.Finally,we investigated the effect of HIF-2αon BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY1485 and the mTOR inhibitor rapamycin.RESULTS The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2αfl/fl mice was lower than that of Hif-2αfl/fl mice under the three intervention conditions.In vitro,Hif-2αfl/fl mouse BMSCs were cultured and treated with the HIF-2αagonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14 d of osteogenic differentiation,BMSCs treated with roxadustat exhibited increased expression of osteogenesis-related genes.The opposite effects were shown for mouse BMSCs treated with the HIF-2αinhibitor PT2399.The mTOR inhibitor rapamycin was used to confirm that HIF-2αregulated BMSC osteogenic and adipogenic differentiation by inhibiting the mTOR pathway.Consequently,there was no significant difference in the hematopoietic function of HSCs between Prx1-Cre;Hif-2αfl/fl and Hif-2αfl/fl mice.CONCLUSION Our study showed that inhibition of HIF-2αdecreases bone mass by inhibiting the osteogenic differentiation and increasing the adipogenic differentiation of BMSCs through inhibition of mTOR signaling in the BM niche.
文摘Background: Renal osteodystrophy (ROD) is a bone disorder resulting from chronic kidney disease (CKD) and related metabolic diseases. Dickkopf-related protein-1 (DKK-1) is critical in regulating bone biology. This study aimed to evaluate the serum DKK-1 level as a bone marker in children with CKD who undergo regular hemodialysis (HD). Subjects and Methods: This case-control study involved 40 children with CKD on HD and 40 healthy children as controls. The study measured serum DKK-1 levels and performed a dual-energy X-ray absorptiometry scan (DEXA) in line with routine laboratory investigations. Results: There was a significant increase in the serum level of DKK-1 in the patient group compared to the control group. The DKK-1 levels were 2540.65 (2215.4 - 2909.2) pg/ml and 1110.45 (885.45 - 1527.65) pg/ml, respectively, with a p-value of less than 0.001. In the hemodialysis group, 25 patients (62.5%) had low bone mineral density (BMD) with a Z-score of under -2.0. Eighteen of these patients had low BMD in both the neck of the femur and lumbar spines. Additionally, there was a significant increase in serum DKK-1 level in patients with low BMD (2567.35 (2303.8 - 3108.1) pg/ml) compared to patients with normal BMD (2454 (1859 - 2820) pg/ml) (p = 0.041). There was also a significant positive correlation between DKK1 level and phosphorus, alkaline phosphatase, and Parathormone serum levels. In conclusion, the study indicates a clear correlation between DKK-1 and BMD in children undergoing maintenance hemodialysis. DKK1 is a promising biomarker for CKD-MBD.
