Ankylosing spondylitis(AS)has a very high disability rate.How to effectively inhibit the formation of new bones has become a difficult point in clinical treatment.In recent years,research has shown that different trea...Ankylosing spondylitis(AS)has a very high disability rate.How to effectively inhibit the formation of new bones has become a difficult point in clinical treatment.In recent years,research has shown that different treatment plans can have an impact on inhibiting new bone formation.In this paper,the different effects of new bone formation in the treatment of AS with traditional Chinese and Western medicine are systematically listed.展开更多
The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorat...The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy.After 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical testing.The results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid biosynthesis.Furthermore,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and microarchitecture.Mechanistically,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.展开更多
The activation of M1 macrophages can be achieved by stimulating them with lipopolysaccharide(LPS) and interferon-γ(IFN-γ). However, M1 can be found under physiological conditions without any pathological stimuli. Th...The activation of M1 macrophages can be achieved by stimulating them with lipopolysaccharide(LPS) and interferon-γ(IFN-γ). However, M1 can be found under physiological conditions without any pathological stimuli. This study aimed to understand the involvement of RANKL-induced M1 macrophages in bone formation compared with pathologically induced macrophages. Fischer rats were used to investigate macrophage distribution in normal and injured femoral condyles in vivo. Bone marrow-derived macrophages(BMDMs) were activated with LPS+IFN-γ and RANKL to achieve M1 activation in vitro. Gene expression related to inflammation, osteoclastogenesis, angiogenesis, and migration was determined by reverse transcription-quantitative polymerase chain reaction(RT-q PCR) and fluorescence-activated cell sorting(FACS). Tissue macrophages showed distinct expression patterns at different bone regions. RANKL was found in close proximity to inducible nitric oxide synthase-positive(iNOS+) cells in vivo, suggesting an association between RANKL expression and i NOS+ cells, especially in trabecular bone. RANKL-induced macrophages showed a different cytokine secretion profile compared with pathologically induced macrophages. Both osteoclasts and M1 macrophages peaked on day 7 during bone healing. RANKL could trigger M1-like macrophages with properties that were different from those of LPS+IFN-γ-induced macrophages. These RANKL-activated M1 macrophages were actively involved in bone formation.展开更多
Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies di...Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies discover that bedridden patients showed osteoporotic T-scores and low bone mineral density,and long-term immobilized patients presented reduced markers of bone formation.However,as bone formation mediated by osteoblast differentiation is a complex process,the underlying molecular mechanism of mechanical stimuli regulating bone formation is still unclear.Recent evidences show that microRNAs(miRNAs)are involved in mechanical stimuli regulating bone formation or osteoblast differentiation.Nevertheless,no direct evidence identifies mechanoresponsive miRNA in both human and animal bones,and clarifies its mechanoresponsive role under different mechanical conditions(e.g.mechanical unloading,reloading,loading).In the current study,we screened for differentially expressed miRNAs in bone specimens of bedridden patients with fractures,then identified that the expression of miR-138-5p,but not the other miRNAs,altered withbedridden time and was negatively correlated with the expression of the bone formation marker genes Alp(alkaline phosphatase).Moreover,miR-138-5p was up-regulated with reduced bone formation during unloading and down-regulated with increased bone formation during reloading in hind4imb unloaded mice.In addition,miR-138-5p was verified to be responsive to different mechanical unloading condition and cyclic mechanical stretch condition in primary osteogenic cells,respectively.Further in vitro data suggested that mechanoresponsive miR-138-5p directly targeted microtubule actin crosslinking factor 1(MACF1)to inhibit osteoblast differentiation.In vivo,we constructed an osteoblastic miR-138-5p transgenic mice model(TG138)with the Runx2promoter,and found that overexpression miR-138-5p supressed bone formation.Moreover,osteoblast-targeted inhibition of miR-138-5p sensitized bone anabolic response to mechanical loading in TG138 mice.Predominantly,the osteoblast-targeted inhibition of miR-138-5p could counteract bone formation reduction induced by hind limb unloading.Taken together,the mechanoresponsive miR-138-5p inhibited bone anabolic response for developing a novel bone anabolic sensitization strategy.展开更多
Objective To investigate plasma leptin concentrations in adolescent female dancers and to determine whether leptin has some effects on their bone mineral density (BMD) and bone turnover markers. Methods Sixty dancers ...Objective To investigate plasma leptin concentrations in adolescent female dancers and to determine whether leptin has some effects on their bone mineral density (BMD) and bone turnover markers. Methods Sixty dancers aged 15-17 years and 77 healthy controls were enrolled in the study. Bone mineral density (BMD) and body composition were detected by dual energy X-ray absorptiometry. Serum leptin concentrations were measured by radioimmunoassay (RIA). Two bone turnover markers, bone-specific alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase(TRACP), were determined by ELISA. Results The dancers had a lower fat mass and a lower leptin level than the controls, while they had a relatively higher BMD of the total body and legs after adjustment for BMI and age. The levels of bone resorption and formation of markers were higher in the dancers than in the controls. Leptin was positively correlated with BMI, body weight, fat mass, and percentage of body fat. In dancers, Leptin was positively correlated with the BMD of the total body and the left leg. However, after adjustment for BMI, no correlation of serum leptin concentrations with BMD values was found in either dancers or controls. Nor correlation was found between leptin and bone turnover markers after adjustment for BMI. Conclusion The leptin profile is different between the controls and the dancers with a lower BMI and a lower fat mass. Circulating plasma leptin level depends on BMI and is not a direct determinant of BMD in Chinese adolescent dancers.展开更多
To study the new bone formation in the bone defect area after implantation, the tetracycline tracing method was used. The results show that new bone formed in 1 month, and the formation rate of new bone was very high ...To study the new bone formation in the bone defect area after implantation, the tetracycline tracing method was used. The results show that new bone formed in 1 month, and the formation rate of new bone was very high (8.164μm/day),considerably faster than that of control groups (3.219μm/day).The new bone grew up quickly and β-TCP particles were surrounded by double fluorescence bands which became more obvious. The new bone formation rate was maximal at 2 months, and then gradually reduced. The rate was steady at 4 months, and then reduced to resembling as the normal physiologic metabolism of bone, which indicated the implanted materials were completely replaced by bone. Calcium phosphate materials had the ability of osteoconduction.展开更多
Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord ...Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury. In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3 K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3 K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3 K/AKT/mTOR pathway.展开更多
The growth and enlargement of jaw cysts are associated with raised intracystic pressure and bone resorption surrounding the cysts.The major bone-resorbing cells are the osteoclasts.They are acting under the influence ...The growth and enlargement of jaw cysts are associated with raised intracystic pressure and bone resorption surrounding the cysts.The major bone-resorbing cells are the osteoclasts.They are acting under the influence of local bone-resorbing factors: prostaglandins,proteinases and cytokines.It was found that positive pressure enhanced the expression of IL-1αmRNA and protein in epithelial cells of odontogenic keratocyst,and increased the secretion of matrix metalloproteinase and PGE2 in a co-culture of odontogenic keratocyst fibroblasts and epithelial cells.However,the signal intensities for IL-1α mRNA and protein in the epithelium were significantly decreased after marsupialization which relived intracystic pressure.Experimental study indicated that intermittent negative pressure could promote osteogenesis in human bone marrow-derived stroma cells(BMSCs) in vitro.We propose a hypothesis that bone formation around the cyst of the jaws would be stimulated by intracystic negative pressure.展开更多
A formalin-treated polyvinyl-alcohol (PVF) sponge is convenient as a scaffold because its configuration is easily modified. However, coating the sponge with an adhesive chemical agent is necessary to attach bone marro...A formalin-treated polyvinyl-alcohol (PVF) sponge is convenient as a scaffold because its configuration is easily modified. However, coating the sponge with an adhesive chemical agent is necessary to attach bone marrow cells (BMCs) to the sponge structure. Moreover, it was considered that a hybrid scaffold composed of a sponge and enveloped cylindrical porous hydroxyapatite (HA) would be convenient. In this study, the effect of leucine (Leu) coating on a PVF sponge was examined for osteogenesis on an HA/PVF hybrid scaffold by rat BMCs (rBMCs). In an in vivo assessment, the sponge immersed in Leu solution (10 mg/ml) was inserted into the hollow center of cylindrical HA. The sponge received 1.5 × 106 rBMCs obtained from male Fischer 344 rats. The hybrid scaffolds were then implanted subcutaneously of syngeneic rats for 6 weeks. In vitro assessment of Leu to hard tissue formation with coating on the well or addition in rBMC culture medium was also performed in a 6-well plate for 2 weeks. In vivo examinations showed the excellent effect of Leu coating on PVF sponge. Leu-coated PVF sponge in the scaffolds showed marked new bone formation in the pores by histological examination. Leu-coated PVF sponge showed a high quantity of osteocalcine (OC). HA might prevent the release of rBMCs from PVF as a barrier. In in vitro examinations, the quantity of OC in rBMC culture with and without the addition of Leu in culture medium showed no significant difference. However, addition of Leu showed significant ALP activity level in culture medium. Leu coating in culture plate wells showed no influence on the quantity of OC. It was concluded from the results that Leu might prevent the emigration of rBMCs to the outside of the scaffold and promote the differentiation of cells to osteoblasts in the scaffold.展开更多
Objective:To study the effect of Chongcao Bushen Capsules on bone turnover markers in patients with diabetic osteoporosis.Methods:107 patients with diabetic osteoporosis treated in the Hospital from December 2016 to N...Objective:To study the effect of Chongcao Bushen Capsules on bone turnover markers in patients with diabetic osteoporosis.Methods:107 patients with diabetic osteoporosis treated in the Hospital from December 2016 to November 2019were enrolled.They were divided into a control group(n=54)and an observation group(n=53)by random number table.The control group was treated with calcium carbonate,and the observation group was treated with Chongcao Bushen Capsules.The treatment effects,TCM syndrome scores,and bone turnover markers[including osteocalcin,type 1 procollagen amino-terminal propeptide(tP1NP),parathyroid hormone(PTH),25-hydroxyvitamin D,andβ-isomerized c-terminal peptide(β-CTx)],and the incidence of adverse reactions in the two groups were observed and compared.Results:After treatment,the total effective rate of treatment in the observation group(94.44%)was higher than that in the control group(73.58%),and the difference was statistically significant(P<0.05).The scores of symptoms including waist and knee weakness,back and waist pain,lower limb weakness,fatigue and tiredness,difficult walking and dizziness in the observation group were shown to be lower than the control group,and the difference was statistically significant(P<0.05).The levels of osteocalcin,PTH,tP1NP,andβ-CTx in the observation group were lower than those in the control group,and the difference was statistically significant(P<0.05).The 25-hydroxyvitamin D in the observation group was higher than the control group,and the difference was statistically significant(P<0.05).Bone density in both male and female in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Conclusion:For patients with diabetic osteoporosis,Chongcao Bushen Capsule can help improve their clinical symptoms,bone density and the level of bone turnover markers.展开更多
Background Body phosphorus metabolism exhibits a circadian rhythm over the 24-h daily cycle.The egg laying behavior makes laying hens a very special model for investigating phosphorus circadian rhythms.There is lack o...Background Body phosphorus metabolism exhibits a circadian rhythm over the 24-h daily cycle.The egg laying behavior makes laying hens a very special model for investigating phosphorus circadian rhythms.There is lack of information about the impact of adjusting phosphate feeding regimen according to daily rhythm on the phosphorus homeostasis and bone remodeling of laying hens.Methods and results Two experiments were conducted.In Exp.1,Hy-Line Brown laying hens(n=45)were sampled according the oviposition cycle(at 0,6,12,and 18 h post-oviposition,and at the next oviposition,respectively;n=9 at each time point).Diurnal rhythms of body calcium/phosphorus ingestions and excretions,serum calcium/phosphorus levels,oviduct uterus calcium transporter expressions,and medullary bone(MB)remodeling were illustrated.In Exp.2,two diets with different phosphorus levels(0.32%and 0.14%non-phytate phosphorus(NPP),respectively)were alternately presented to the laying hens.Briefly,four phosphorus feeding regimens in total(each included 6 replicates of 5 hens):(1)fed 0.32%NPP at both 09:00 and 17:00;(2)fed 0.32%NPP at 09:00 and 0.14%NPP at 17:00;(3)fed 0.14%NPP at 09:00 and 0.32%NPP at 17:00;(4)fed 0.14%NPP at both 09:00 and 17:00.As a result,the regimen fed 0.14%NPP at 09:00 and 0.32%NPP at 17:00,which was designed to strengthen intrinsic phosphate circadian rhythms according to the findings in Exp.1,enhanced(P<0.05)MB remodeling(indicated by histological images,serum markers and bone mineralization gene expressions),elevated(P<0.05)oviduct uterus calcium transportation(indicated by transient receptor potential vanilloid 6 protein expression),and subsequently increased(P<0.05)eggshell thickness,eggshell strength,egg specific gravity and eggshell index in laying hens.Conclusions These results underscore the importance of manipulating the sequence of daily phosphorus ingestion,instead of simply controlling dietary phosphate concentrations,in modifying the bone remodeling process.Body phosphorus rhythms will need to be maintained during the daily eggshell calcification cycle.展开更多
Background:The training program promoted improvements of jump abilities throughout the musculoskeletal system including bone markers.The aim of this study is to examine both the acute and chronic response of bone mark...Background:The training program promoted improvements of jump abilities throughout the musculoskeletal system including bone markers.The aim of this study is to examine both the acute and chronic response of bone markers to resistance training program.Methods:Ten female students(age:18±0.7 years,body mass:63±3.6 kg;height:164±5.2 cm)participated in this study.They were recruited for a back-squat training program for 12 weeks,two days/week.The full-back squat protocol consisted of 3–5 sets×3–8 repetitions at 45–55%one repetition maximum.Testing sessions included a 5 jump test(5JT),standing long jump(SLJ),drop jump(DJ),and vertical jump(VJ).Results:Substantial improvements in all testing jumps(5JT:∆10%;P=0.000;ES=1.72;SLJ:∆7%;P=0.000;ES=1.33;DJ:∆11%;P=0.000;ES=0.72;VJ:∆20%;P=0.000;ES=1.84)were found during post program in comparison to pre-program results.Moreover,a significant change(P≤0.05)of bone markers during post-exercise compared to pre-exercise either before or after the training program.Only collagen type I carboxy-terminal peptide(CICP)levels elevated after the training program(pre-exercise only)compared to former levels.Conclusion:12 weeks of back-squat training program resulted greater acute improvements of jump abilities with adaptation in all musculoskeletal system including bone formation.展开更多
To benefit tissue removal and postoperative rehabilitation,increased efficiency and accuracy and reduced operating force are strongly required in the osteotomy.A novel elliptical vibration cutting(EVC)has been introdu...To benefit tissue removal and postoperative rehabilitation,increased efficiency and accuracy and reduced operating force are strongly required in the osteotomy.A novel elliptical vibration cutting(EVC)has been introduced for bone cutting compared with conventional cutting(CC)in this paper.With the assistance of high-speed microscope imaging and the dynamometer,the material removals of cortical bone and their cutting forces from two cutting regimes were recorded and analysed comprehensively,which clearly demonstrated the chip morphology improvement and the average cutting force reduction in the EVC process.It also revealed that the elliptical vibration of the cutting tool could promote fracture propagation along the shear direction.These new findings will be of important theoretical and practical values to apply the innovative EVC process to the surgical procedures of the osteotomy.展开更多
BACKGROUND Bones are one of the most common target organs for cancer metastasis.Early evaluation of bone metastasis(BM)status is clinically significant.Cancer patients often experience a hypercoagulable state.AIM To e...BACKGROUND Bones are one of the most common target organs for cancer metastasis.Early evaluation of bone metastasis(BM)status is clinically significant.Cancer patients often experience a hypercoagulable state.AIM To evaluate the correlation between coagulation indicators and the burden of BM in gastric cancer(GC).METHODS We conducted a single-center retrospective study and enrolled 454 patients.Clinical information including routine blood examination and coagulation markers were collected before any treatment.Patients were grouped according to the status of BM.Receiver operating characteristic curves were used to assess diagnostic performance and determine the optimal cutoff values of the above indicators.Cutoff values,sensitivity and specificity were based on the maximum Youden index.Univariate and multivariate logistic regression analyses were used to evaluate the relationships between biomarkers and BM.RESULTS Of the 454 enrolled patients,191 patients were diagnosed with BM.The receiver operating characteristic curve analysis suggested that prothrombin time(PT)Wang X et al.Coagulation indicators predict bone metastasis WJGO https://www.wjgnet.com 1254 July 15,2023 Volume 15 Issue 7[cutoff:13.25;sensitivity:0.651;specificity:0.709;area under receiver operating characteristic curve(AUC)=0.738],activated partial thromboplastin time(aPTT)(cutoff:35.15;sensitivity:0.640;specificity:0.640;AUC=0.678)and fibrin degradation products(FDP)(cutoff:2.75;sensitivity:0.668;specificity:0.801;AUC=0.768)act as novel predictors for BM.Based on multivariate logistic regression analysis,the results showed the independent correlation between PT[odds ratio(OR):3.16;95%confidence interval(CI):1.612-6.194;P=0.001],aPTT(OR:2.234;95%CI:1.157-4.313;P=0.017)and FDP(OR:3.17;95%CI:1.637-6.139;P=0.001)and BM in patients with GC.Moreover,age,carcinoembryonic antigen,erythrocyte and globulin were found to be significantly associated with BM.CONCLUSION Coagulation markers,namely PT,aPTT and FDP,might be potential predictors for screening BM in patients with GC.展开更多
目的了解骨质疏松性椎体压缩骨折二级预防失败患者骨代谢指标及骨密度的特点。方法选择2015年1月至2020年1月在我院骨科因骨质疏松性椎体压缩骨折行2次或2次以上手术治疗的患者为观察组研究对象,共65例,同时选择同时期行手术治疗的非多...目的了解骨质疏松性椎体压缩骨折二级预防失败患者骨代谢指标及骨密度的特点。方法选择2015年1月至2020年1月在我院骨科因骨质疏松性椎体压缩骨折行2次或2次以上手术治疗的患者为观察组研究对象,共65例,同时选择同时期行手术治疗的非多次脊柱压缩骨折患者219例作为配对资料对照组,回顾性分析这284例患者临床资料,记录其术前骨代谢标志物水平及骨密度(bone mineral density,BMD)结果并进行两组患者间比较。结果观察组患者骨代谢标志物中人血清和血浆中的总I型前胶原氨基端肽(tP1NP)、N⁃MID骨钙素(OCN)以及血清25⁃羟维生素D(25⁃hydroxy vitamin D,25OHD)水平与对照组相比差异无统计学意义(P>0.05),骨代谢标志物I型胶原羧基端肽β特殊序列(β⁃CTX)水平明显高于对照组(P<0.05)。两组患者髋部BMD值、股骨颈BMD值差异无统计学意义(P>0.05),观察组腰椎BMD值明显低于对照组(P<0.05)。结论骨质疏松性椎体压缩骨折二级预防失败患者具有更为活跃的骨吸收状态及更低的腰椎骨密度。展开更多
基金Supported by the National Natural Science Foundation of China(82205105).
文摘Ankylosing spondylitis(AS)has a very high disability rate.How to effectively inhibit the formation of new bones has become a difficult point in clinical treatment.In recent years,research has shown that different treatment plans can have an impact on inhibiting new bone formation.In this paper,the different effects of new bone formation in the treatment of AS with traditional Chinese and Western medicine are systematically listed.
基金supported by the National Natural Science Foundation of China (32072191)Daxing District Major Scientific and Technological Achievements Transformation Project (2020006)+1 种基金Beijing Innovation Team Project of Livestock Industry Technology SystemBeijing Science and Technology Special Project (Z201100002620005)。
文摘The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy.After 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical testing.The results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid biosynthesis.Furthermore,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and microarchitecture.Mechanistically,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.
基金supported by the CSC (China Scholarship Council)-QUT (Queensland University of Technology) PhD Scholarship awarded to Ms Rong Huangthe Institute of Health and Biomedical Innovation Early Career Researcher Scheme Funding awarded to Dr Yinghong Zhou
文摘The activation of M1 macrophages can be achieved by stimulating them with lipopolysaccharide(LPS) and interferon-γ(IFN-γ). However, M1 can be found under physiological conditions without any pathological stimuli. This study aimed to understand the involvement of RANKL-induced M1 macrophages in bone formation compared with pathologically induced macrophages. Fischer rats were used to investigate macrophage distribution in normal and injured femoral condyles in vivo. Bone marrow-derived macrophages(BMDMs) were activated with LPS+IFN-γ and RANKL to achieve M1 activation in vitro. Gene expression related to inflammation, osteoclastogenesis, angiogenesis, and migration was determined by reverse transcription-quantitative polymerase chain reaction(RT-q PCR) and fluorescence-activated cell sorting(FACS). Tissue macrophages showed distinct expression patterns at different bone regions. RANKL was found in close proximity to inducible nitric oxide synthase-positive(iNOS+) cells in vivo, suggesting an association between RANKL expression and i NOS+ cells, especially in trabecular bone. RANKL-induced macrophages showed a different cytokine secretion profile compared with pathologically induced macrophages. Both osteoclasts and M1 macrophages peaked on day 7 during bone healing. RANKL could trigger M1-like macrophages with properties that were different from those of LPS+IFN-γ-induced macrophages. These RANKL-activated M1 macrophages were actively involved in bone formation.
基金supported by the National Natural Science Foundation of China ( 31570940,81772017)
文摘Mechanical stimuli play an essential role in maintaining bone remodeling and skeletal integrity.Meanwhile,bone can respond to the changes of mechanical condition to adjust its mass and architecture.Clinical studies discover that bedridden patients showed osteoporotic T-scores and low bone mineral density,and long-term immobilized patients presented reduced markers of bone formation.However,as bone formation mediated by osteoblast differentiation is a complex process,the underlying molecular mechanism of mechanical stimuli regulating bone formation is still unclear.Recent evidences show that microRNAs(miRNAs)are involved in mechanical stimuli regulating bone formation or osteoblast differentiation.Nevertheless,no direct evidence identifies mechanoresponsive miRNA in both human and animal bones,and clarifies its mechanoresponsive role under different mechanical conditions(e.g.mechanical unloading,reloading,loading).In the current study,we screened for differentially expressed miRNAs in bone specimens of bedridden patients with fractures,then identified that the expression of miR-138-5p,but not the other miRNAs,altered withbedridden time and was negatively correlated with the expression of the bone formation marker genes Alp(alkaline phosphatase).Moreover,miR-138-5p was up-regulated with reduced bone formation during unloading and down-regulated with increased bone formation during reloading in hind4imb unloaded mice.In addition,miR-138-5p was verified to be responsive to different mechanical unloading condition and cyclic mechanical stretch condition in primary osteogenic cells,respectively.Further in vitro data suggested that mechanoresponsive miR-138-5p directly targeted microtubule actin crosslinking factor 1(MACF1)to inhibit osteoblast differentiation.In vivo,we constructed an osteoblastic miR-138-5p transgenic mice model(TG138)with the Runx2promoter,and found that overexpression miR-138-5p supressed bone formation.Moreover,osteoblast-targeted inhibition of miR-138-5p sensitized bone anabolic response to mechanical loading in TG138 mice.Predominantly,the osteoblast-targeted inhibition of miR-138-5p could counteract bone formation reduction induced by hind limb unloading.Taken together,the mechanoresponsive miR-138-5p inhibited bone anabolic response for developing a novel bone anabolic sensitization strategy.
基金supported by the China Research Grant 2006 from Danone Institute (No. DIC 2006-14)
文摘Objective To investigate plasma leptin concentrations in adolescent female dancers and to determine whether leptin has some effects on their bone mineral density (BMD) and bone turnover markers. Methods Sixty dancers aged 15-17 years and 77 healthy controls were enrolled in the study. Bone mineral density (BMD) and body composition were detected by dual energy X-ray absorptiometry. Serum leptin concentrations were measured by radioimmunoassay (RIA). Two bone turnover markers, bone-specific alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase(TRACP), were determined by ELISA. Results The dancers had a lower fat mass and a lower leptin level than the controls, while they had a relatively higher BMD of the total body and legs after adjustment for BMI and age. The levels of bone resorption and formation of markers were higher in the dancers than in the controls. Leptin was positively correlated with BMI, body weight, fat mass, and percentage of body fat. In dancers, Leptin was positively correlated with the BMD of the total body and the left leg. However, after adjustment for BMI, no correlation of serum leptin concentrations with BMD values was found in either dancers or controls. Nor correlation was found between leptin and bone turnover markers after adjustment for BMI. Conclusion The leptin profile is different between the controls and the dancers with a lower BMI and a lower fat mass. Circulating plasma leptin level depends on BMI and is not a direct determinant of BMD in Chinese adolescent dancers.
文摘To study the new bone formation in the bone defect area after implantation, the tetracycline tracing method was used. The results show that new bone formed in 1 month, and the formation rate of new bone was very high (8.164μm/day),considerably faster than that of control groups (3.219μm/day).The new bone grew up quickly and β-TCP particles were surrounded by double fluorescence bands which became more obvious. The new bone formation rate was maximal at 2 months, and then gradually reduced. The rate was steady at 4 months, and then reduced to resembling as the normal physiologic metabolism of bone, which indicated the implanted materials were completely replaced by bone. Calcium phosphate materials had the ability of osteoconduction.
基金supported by the National Key R&D Program of China,No.2020YFC2008502 (to QW)the National Natural Science Foundation of China,No. 82172534 (to QW)。
文摘Although many therapeutic interventions have shown promise in treating spinal cord injury, focusing on a single aspect of repair cannot achieve successful and functional regeneration in patients following spinal cord injury. In this study, we applied a combinatorial approach for treating spinal cord injury involving neuroprotection and rehabilitation, exploiting cell transplantation and functional sensorimotor training to promote nerve regeneration and functional recovery. Here, we used a mouse model of thoracic contusive spinal cord injury to investigate whether the combination of bone marrow mesenchymal stem cell transplantation and exercise training has a synergistic effect on functional restoration. Locomotor function was evaluated by the Basso Mouse Scale, horizontal ladder test, and footprint analysis. Magnetic resonance imaging, histological examination, transmission electron microscopy observation, immunofluorescence staining, and western blotting were performed 8 weeks after spinal cord injury to further explore the potential mechanism behind the synergistic repair effect. In vivo, the combination of bone marrow mesenchymal stem cell transplantation and exercise showed a better therapeutic effect on motor function than the single treatments. Further investigations revealed that the combination of bone marrow mesenchymal stem cell transplantation and exercise markedly reduced fibrotic scar tissue, protected neurons, and promoted axon and myelin protection. Additionally, the synergistic effects of bone marrow mesenchymal stem cell transplantation and exercise on spinal cord injury recovery occurred via the PI3 K/AKT/mTOR pathway. In vitro, experimental evidence from the PC12 cell line and primary cortical neuron culture also demonstrated that blocking of the PI3 K/AKT/mTOR pathway would aggravate neuronal damage. Thus, bone marrow mesenchymal stem cell transplantation combined with exercise training can effectively restore motor function after spinal cord injury by activating the PI3 K/AKT/mTOR pathway.
文摘The growth and enlargement of jaw cysts are associated with raised intracystic pressure and bone resorption surrounding the cysts.The major bone-resorbing cells are the osteoclasts.They are acting under the influence of local bone-resorbing factors: prostaglandins,proteinases and cytokines.It was found that positive pressure enhanced the expression of IL-1αmRNA and protein in epithelial cells of odontogenic keratocyst,and increased the secretion of matrix metalloproteinase and PGE2 in a co-culture of odontogenic keratocyst fibroblasts and epithelial cells.However,the signal intensities for IL-1α mRNA and protein in the epithelium were significantly decreased after marsupialization which relived intracystic pressure.Experimental study indicated that intermittent negative pressure could promote osteogenesis in human bone marrow-derived stroma cells(BMSCs) in vitro.We propose a hypothesis that bone formation around the cyst of the jaws would be stimulated by intracystic negative pressure.
文摘A formalin-treated polyvinyl-alcohol (PVF) sponge is convenient as a scaffold because its configuration is easily modified. However, coating the sponge with an adhesive chemical agent is necessary to attach bone marrow cells (BMCs) to the sponge structure. Moreover, it was considered that a hybrid scaffold composed of a sponge and enveloped cylindrical porous hydroxyapatite (HA) would be convenient. In this study, the effect of leucine (Leu) coating on a PVF sponge was examined for osteogenesis on an HA/PVF hybrid scaffold by rat BMCs (rBMCs). In an in vivo assessment, the sponge immersed in Leu solution (10 mg/ml) was inserted into the hollow center of cylindrical HA. The sponge received 1.5 × 106 rBMCs obtained from male Fischer 344 rats. The hybrid scaffolds were then implanted subcutaneously of syngeneic rats for 6 weeks. In vitro assessment of Leu to hard tissue formation with coating on the well or addition in rBMC culture medium was also performed in a 6-well plate for 2 weeks. In vivo examinations showed the excellent effect of Leu coating on PVF sponge. Leu-coated PVF sponge in the scaffolds showed marked new bone formation in the pores by histological examination. Leu-coated PVF sponge showed a high quantity of osteocalcine (OC). HA might prevent the release of rBMCs from PVF as a barrier. In in vitro examinations, the quantity of OC in rBMC culture with and without the addition of Leu in culture medium showed no significant difference. However, addition of Leu showed significant ALP activity level in culture medium. Leu coating in culture plate wells showed no influence on the quantity of OC. It was concluded from the results that Leu might prevent the emigration of rBMCs to the outside of the scaffold and promote the differentiation of cells to osteoblasts in the scaffold.
基金Traditional Chinese medicine research project of Hebei administration of traditional Chinese medicine(No.2016092)。
文摘Objective:To study the effect of Chongcao Bushen Capsules on bone turnover markers in patients with diabetic osteoporosis.Methods:107 patients with diabetic osteoporosis treated in the Hospital from December 2016 to November 2019were enrolled.They were divided into a control group(n=54)and an observation group(n=53)by random number table.The control group was treated with calcium carbonate,and the observation group was treated with Chongcao Bushen Capsules.The treatment effects,TCM syndrome scores,and bone turnover markers[including osteocalcin,type 1 procollagen amino-terminal propeptide(tP1NP),parathyroid hormone(PTH),25-hydroxyvitamin D,andβ-isomerized c-terminal peptide(β-CTx)],and the incidence of adverse reactions in the two groups were observed and compared.Results:After treatment,the total effective rate of treatment in the observation group(94.44%)was higher than that in the control group(73.58%),and the difference was statistically significant(P<0.05).The scores of symptoms including waist and knee weakness,back and waist pain,lower limb weakness,fatigue and tiredness,difficult walking and dizziness in the observation group were shown to be lower than the control group,and the difference was statistically significant(P<0.05).The levels of osteocalcin,PTH,tP1NP,andβ-CTx in the observation group were lower than those in the control group,and the difference was statistically significant(P<0.05).The 25-hydroxyvitamin D in the observation group was higher than the control group,and the difference was statistically significant(P<0.05).Bone density in both male and female in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).Conclusion:For patients with diabetic osteoporosis,Chongcao Bushen Capsule can help improve their clinical symptoms,bone density and the level of bone turnover markers.
基金supported by National Natural Science Foundation of China (32172759)Shaanxi Provincial Science and Technology Department (2022QFY11-05,2021KJXX-97,2021TD-30).
文摘Background Body phosphorus metabolism exhibits a circadian rhythm over the 24-h daily cycle.The egg laying behavior makes laying hens a very special model for investigating phosphorus circadian rhythms.There is lack of information about the impact of adjusting phosphate feeding regimen according to daily rhythm on the phosphorus homeostasis and bone remodeling of laying hens.Methods and results Two experiments were conducted.In Exp.1,Hy-Line Brown laying hens(n=45)were sampled according the oviposition cycle(at 0,6,12,and 18 h post-oviposition,and at the next oviposition,respectively;n=9 at each time point).Diurnal rhythms of body calcium/phosphorus ingestions and excretions,serum calcium/phosphorus levels,oviduct uterus calcium transporter expressions,and medullary bone(MB)remodeling were illustrated.In Exp.2,two diets with different phosphorus levels(0.32%and 0.14%non-phytate phosphorus(NPP),respectively)were alternately presented to the laying hens.Briefly,four phosphorus feeding regimens in total(each included 6 replicates of 5 hens):(1)fed 0.32%NPP at both 09:00 and 17:00;(2)fed 0.32%NPP at 09:00 and 0.14%NPP at 17:00;(3)fed 0.14%NPP at 09:00 and 0.32%NPP at 17:00;(4)fed 0.14%NPP at both 09:00 and 17:00.As a result,the regimen fed 0.14%NPP at 09:00 and 0.32%NPP at 17:00,which was designed to strengthen intrinsic phosphate circadian rhythms according to the findings in Exp.1,enhanced(P<0.05)MB remodeling(indicated by histological images,serum markers and bone mineralization gene expressions),elevated(P<0.05)oviduct uterus calcium transportation(indicated by transient receptor potential vanilloid 6 protein expression),and subsequently increased(P<0.05)eggshell thickness,eggshell strength,egg specific gravity and eggshell index in laying hens.Conclusions These results underscore the importance of manipulating the sequence of daily phosphorus ingestion,instead of simply controlling dietary phosphate concentrations,in modifying the bone remodeling process.Body phosphorus rhythms will need to be maintained during the daily eggshell calcification cycle.
文摘Background:The training program promoted improvements of jump abilities throughout the musculoskeletal system including bone markers.The aim of this study is to examine both the acute and chronic response of bone markers to resistance training program.Methods:Ten female students(age:18±0.7 years,body mass:63±3.6 kg;height:164±5.2 cm)participated in this study.They were recruited for a back-squat training program for 12 weeks,two days/week.The full-back squat protocol consisted of 3–5 sets×3–8 repetitions at 45–55%one repetition maximum.Testing sessions included a 5 jump test(5JT),standing long jump(SLJ),drop jump(DJ),and vertical jump(VJ).Results:Substantial improvements in all testing jumps(5JT:∆10%;P=0.000;ES=1.72;SLJ:∆7%;P=0.000;ES=1.33;DJ:∆11%;P=0.000;ES=0.72;VJ:∆20%;P=0.000;ES=1.84)were found during post program in comparison to pre-program results.Moreover,a significant change(P≤0.05)of bone markers during post-exercise compared to pre-exercise either before or after the training program.Only collagen type I carboxy-terminal peptide(CICP)levels elevated after the training program(pre-exercise only)compared to former levels.Conclusion:12 weeks of back-squat training program resulted greater acute improvements of jump abilities with adaptation in all musculoskeletal system including bone formation.
基金Supported by National Natural Science Foundation of China (Grant Nos.52005199 and 42241149)Shenzhen Fundamental Research Program (Grant Nos.JCYJ20200109150425085 and JCYJ20220818102601004)+2 种基金Shenzhen Science and Technology Program (Grant Nos.JSGG20201103100001004 and JSGG20220831105800001)Research Development Program of China (Grant No.2022YFB4602502)Knowledge Innovation Program of Wuhan-Basic Research (Grant No.2022010801010203)。
文摘To benefit tissue removal and postoperative rehabilitation,increased efficiency and accuracy and reduced operating force are strongly required in the osteotomy.A novel elliptical vibration cutting(EVC)has been introduced for bone cutting compared with conventional cutting(CC)in this paper.With the assistance of high-speed microscope imaging and the dynamometer,the material removals of cortical bone and their cutting forces from two cutting regimes were recorded and analysed comprehensively,which clearly demonstrated the chip morphology improvement and the average cutting force reduction in the EVC process.It also revealed that the elliptical vibration of the cutting tool could promote fracture propagation along the shear direction.These new findings will be of important theoretical and practical values to apply the innovative EVC process to the surgical procedures of the osteotomy.
文摘BACKGROUND Bones are one of the most common target organs for cancer metastasis.Early evaluation of bone metastasis(BM)status is clinically significant.Cancer patients often experience a hypercoagulable state.AIM To evaluate the correlation between coagulation indicators and the burden of BM in gastric cancer(GC).METHODS We conducted a single-center retrospective study and enrolled 454 patients.Clinical information including routine blood examination and coagulation markers were collected before any treatment.Patients were grouped according to the status of BM.Receiver operating characteristic curves were used to assess diagnostic performance and determine the optimal cutoff values of the above indicators.Cutoff values,sensitivity and specificity were based on the maximum Youden index.Univariate and multivariate logistic regression analyses were used to evaluate the relationships between biomarkers and BM.RESULTS Of the 454 enrolled patients,191 patients were diagnosed with BM.The receiver operating characteristic curve analysis suggested that prothrombin time(PT)Wang X et al.Coagulation indicators predict bone metastasis WJGO https://www.wjgnet.com 1254 July 15,2023 Volume 15 Issue 7[cutoff:13.25;sensitivity:0.651;specificity:0.709;area under receiver operating characteristic curve(AUC)=0.738],activated partial thromboplastin time(aPTT)(cutoff:35.15;sensitivity:0.640;specificity:0.640;AUC=0.678)and fibrin degradation products(FDP)(cutoff:2.75;sensitivity:0.668;specificity:0.801;AUC=0.768)act as novel predictors for BM.Based on multivariate logistic regression analysis,the results showed the independent correlation between PT[odds ratio(OR):3.16;95%confidence interval(CI):1.612-6.194;P=0.001],aPTT(OR:2.234;95%CI:1.157-4.313;P=0.017)and FDP(OR:3.17;95%CI:1.637-6.139;P=0.001)and BM in patients with GC.Moreover,age,carcinoembryonic antigen,erythrocyte and globulin were found to be significantly associated with BM.CONCLUSION Coagulation markers,namely PT,aPTT and FDP,might be potential predictors for screening BM in patients with GC.
文摘目的了解骨质疏松性椎体压缩骨折二级预防失败患者骨代谢指标及骨密度的特点。方法选择2015年1月至2020年1月在我院骨科因骨质疏松性椎体压缩骨折行2次或2次以上手术治疗的患者为观察组研究对象,共65例,同时选择同时期行手术治疗的非多次脊柱压缩骨折患者219例作为配对资料对照组,回顾性分析这284例患者临床资料,记录其术前骨代谢标志物水平及骨密度(bone mineral density,BMD)结果并进行两组患者间比较。结果观察组患者骨代谢标志物中人血清和血浆中的总I型前胶原氨基端肽(tP1NP)、N⁃MID骨钙素(OCN)以及血清25⁃羟维生素D(25⁃hydroxy vitamin D,25OHD)水平与对照组相比差异无统计学意义(P>0.05),骨代谢标志物I型胶原羧基端肽β特殊序列(β⁃CTX)水平明显高于对照组(P<0.05)。两组患者髋部BMD值、股骨颈BMD值差异无统计学意义(P>0.05),观察组腰椎BMD值明显低于对照组(P<0.05)。结论骨质疏松性椎体压缩骨折二级预防失败患者具有更为活跃的骨吸收状态及更低的腰椎骨密度。
