[Objectives]To explore the protective effect and molecular mechanism of Shui People s Classic Prescription Jipei Dilong Ointment on knee osteoarthritis in rats.[Methods]72 SPF male SD rats were divided into control gr...[Objectives]To explore the protective effect and molecular mechanism of Shui People s Classic Prescription Jipei Dilong Ointment on knee osteoarthritis in rats.[Methods]72 SPF male SD rats were divided into control group,model group,Jipei Dilong Ointment high,medium and low dose groups,and positive drug Diclofenac group,with 12 rats in each group.Except the control group,all other groups were injected with 0.2 mL of 2%papain and 0.3%L-cysteine mixture into knee joint cavity to establish osteoarthritis model,while the control group was injected with the same amount of normal saline.The Lequesne MG score was used to determine the success of the model.After successful modeling,external administration was given for 4 weeks.The histopathological changes in articular cartilage and synovium were observed by HE staining;the levels of TNF-α,IL-1βand COX-2 in serum were detected by ELISA,and the relative expression of MMP-9 and TIMP-1 mRNA in cartilage was detected by qRT-PCR;the relative expression of MMP-9,TIMP-1,TLR4,MyD88 and NF-κB in rat cartilage was detected by Western-blot.[Results]Compared with the model group,Jipei Dilong Ointment could significantly reduce the Lequesne MG score and Mankin s score of arthritic rats(P<0.01);significantly improve the pathological changes in articular cartilage and synovium,reduce tissue edema,necrosis,inflammatory cell infiltration and fibrous tissue proliferation;reduce the expression of MMP-9 mRNA(P<0.01)in different degrees and increase the expression of TIMP-1 mRNA(P<0.01);reduce the relative expression of MMP-9,TLR4,MyD88 and NF-κB protein in different degrees(P<0.01),and significantly increase the relative expression of TIMP-1 protein in cartilage(P<0.01).[Conclusions]Jipei Dilong Ointment can improve the joint injury of osteoarthritis rats,and the mechanism may be related to the regulation of TLR4/MyD88/NF-κB signaling pathway and the ratio of MMP-9/TIMP-1.展开更多
This study is designed to determine whether the outermost layer of articular cartilage is deficient in Osteoarthritis (OA). Phospholipids present in healthy and osteoarthritis (OA) synovial fluid show significant diff...This study is designed to determine whether the outermost layer of articular cartilage is deficient in Osteoarthritis (OA). Phospholipids present in healthy and osteoarthritis (OA) synovial fluid show significant differences in their concentration. While examining the surface properties of OA joints, we found that OA PLs molecules cannot support lubrication, and increased friction was observed. Our lubrication mechanism was based on a surface active phospholipids (SAPL) multibilayer which in OA condition was deactivated and removed from the cartilage surface under OA conditions. Cartilage wettability study clearly demonstrated a significant decrease in hydrophobicity, the contact angle, θ (theta), dropping from 103° from bovine healthy cartilage to 65° in surface partially depleted and 35.1° for completely depleted surface. These results are discussed in the context that surface active phospholipid (SAPL) and lubricin, each has specific roles in a lamellar-repulsive lubrication system. However, deactivated phospholipid molecules are major indicator of cartilage wear (model) introduced in this study.展开更多
Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are ...Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial meniscus.Genetic mouse models mimicking sustained Akt signaling in articular chondrocytes via PTEN deficiency driven by either Col2a1-Cre or Col2a1-Cre^(ERT2) developed OA, whereas restriction of Akt signaling reversed the OA phenotypes in PTEN-deficient mice.Mechanistically, prolonged activation of Akt signaling caused an accumulation of reactive oxygen species and triggered chondrocyte senescence as well as a senescence-associated secretory phenotype, whereas chronic administration of the antioxidant N-acetylcysteine suppressed chondrocyte senescence and mitigated OA progression in PTEN-deficient mice. Therefore,inhibition of Akt signaling by PTEN is required for the maintenance of articular cartilage. Disrupted Akt signaling in articular chondrocytes triggers oxidative stress-induced chondrocyte senescence and causes OA.展开更多
The sEMG signals are collected from the vastus lateralis,vastus medialis,biceps femoris,and semitendinosus of lower extremity during level walking among control subjects and knee osteoarthritis (OA) patients,the latte...The sEMG signals are collected from the vastus lateralis,vastus medialis,biceps femoris,and semitendinosus of lower extremity during level walking among control subjects and knee osteoarthritis (OA) patients,the latter including mild,moderate and severe degree.The 5-fold cross-validation is used to measure the accuracy of the proposed analysis algorithm on collected sEMG recordings.For comparison,the more classical feature vectors of form factor,degree of skewness,kurtosis,and wavelet entropy are also tested.In experiment,the normalized energy ratio and marginal spectrum ratio achieve larger accuracy than the other features for all the four muscular groups.Moreover the accuracy of vastus medialis and biceps femoris are larger than that of vastus lateralis and semitendinosus.These results suggest that the normalized energy ratio and marginal spectrum ratio via the analysis of knee sEMG signals by HHT can server as characteristic parameters to easily classify osteoarthritis with noninvasive method.The more important muscular groups for maintaining the knee joint function are medialis and biceps femoris;as a result of that they should be exercise especially for rehabilitation.展开更多
The pathogenesis of equine Osteoarthritis(OA) is more complex, and the disease in the early stage is not easy to be found, therefore, the early diagnosis and treatment are very important. Based on this, this experimen...The pathogenesis of equine Osteoarthritis(OA) is more complex, and the disease in the early stage is not easy to be found, therefore, the early diagnosis and treatment are very important. Based on this, this experiment established OA model induced by equine, aimed to study the changes of contents of Matrix Metalloproteinases-3(MMP-3), Matrix Metalloproteinases-13(MMP-13), Aggrecanase(ADAMTS-5), Hyaluronic Acid(HA) and Osteocalcin(OCN) in synovial fluid, and establish rapid diagnostic technique for the equine OA. Thirteen Mongolian equines were used in these induction studies. Equines were randomly divided into two groups: the experimental group contained eight equines and the control group contained five equines. The experimental group was to build the equine osteoarthritis model. The induction was done through Intra-articular(IA) injection of 2 m L Amphotericin-B in equines' left carpal joints. The equine of the control group was injected into 2 m L physiological saline in equines' left carpal joints. Synovial fluid was collected every week until the 9th week. The contents of MMP-3, MMP-13, ADAMTS-5, HA and OCN in synovial fluid were evaluated by using ELISA kits. Equine OA model, compared with the control group, starting from the 1st to the 2nd week after induction model, the content of MMP-3, MMP-13, ADAMTS-5, HA and OCN tended to increase, but there was no significant increase, from the 2nd to the 3rd week they significantly increased(p<0.05) and kept increasing trend until the 9th week. In OA model, MMP-3, MMP-13, ADAMTS-5, HA and OCN showed a rising trend in joint fluid, which would accelerate the cartilage, subchondral bone degradation and metabolism of these proteases increased, and ADAMTS-5 and HA in the early stage increased significantly.展开更多
Healthy cartilage is a water-filled super lubricious tissue.Collagen type II provides it structural stability,and proteoglycans absorb water to keep the cartilage in a swollen condition,providing it the ability to cre...Healthy cartilage is a water-filled super lubricious tissue.Collagen type II provides it structural stability,and proteoglycans absorb water to keep the cartilage in a swollen condition,providing it the ability to creep and provide weeping lubrication.Osteoarthritis(OA)is a degenerative and debilitating disorder of diarthrodial joints,where articular cartilage damage originates from enzymatic degradation and mechanical damage(wear).The objective of this research is to observe the level of cartilage damage present in knee arthroplasty patients and to understand the friction and creep behavior of enzymatically degraded bovine cartilage in vitro.Lateral(Lat)and medial(Med)condylar cartilages from OA patients undergoing total knee arthroplasty showed signs of enzymatic degradation and mechanical damage.Bovine cartilages were exposed to collagenase III and chondroitinase ABC to degrade collagen and proteoglycans,respectively.The loss of proteoglycans or collagen network and morphological changes were observed through histology and the atomic force microscope(AFM),respectively.A significant effect on creep due to enzymatic treatment was not observed.But the enzymatic treatment was found to significantly decrease the coefficient of friction(COF)at 4 N,while higher COF was shown from chondroitinase ABC degraded cartilage at 40 N.Collagenase III treatment leads to the release of intact proteoglycans at the sliding interface,while chondroitinase ABC treatment leads to the loss of chondroitin sulfate(CS)from the proteoglycans.Chondroitinase ABC-digested bovine cartilage mimicked patient samples the best because of the similar distributions of proteoglycans,collagen network,and friction behavior.展开更多
Studying the lubrication properties of osteoarthritis(OA)synovial fluid(SF)enables an understanding of the boundary lubrication joint,mobility,and friction.However,tribology has never been combined with the clinical r...Studying the lubrication properties of osteoarthritis(OA)synovial fluid(SF)enables an understanding of the boundary lubrication joint,mobility,and friction.However,tribology has never been combined with the clinical reality of the presence of worn particles within the synovial fluid and how they affect the osteoarthritic joints.Part of the problem relates to the tribology methods studying friction by applying inadequate pin-on-disc techniques.In this study,synovial fluid with and without worn particles was studied using a customized tribometer.This method enables opening the contact at the end of each cycle and simulates better contact conditions of a natural knee joint and can thus be applied for evaluating the severity of joint OA and the treatment given to the patient.展开更多
The skeletal system is a dynamically balanced system, which undergoes continuous bone resorption and formation to maintain bone matrix homeostasis. As an important ADP-ribosylase and NAD+-dependent deacylase, SIRT6 (S...The skeletal system is a dynamically balanced system, which undergoes continuous bone resorption and formation to maintain bone matrix homeostasis. As an important ADP-ribosylase and NAD+-dependent deacylase, SIRT6 (SIR2-like protein 6) is widely expressed on various kinds of bone cells, such as chondrocytes, osteoblasts, osteoclasts. The aberration of SIRT6 impairs gene expression (e.g., NF-κB and Wnt target genes) and cellular functions (e.g., DNA repair, glucose and lipid metabolism, telomeric maintenance), which disturbs the dynamic balance and ultimately leads to several bone-related diseases. In this review, we summarize the critical roles of SIRT6 in the onset and progression of bone-related diseases including osteoporosis, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, as well as the relevant signaling pathways. In addition, we discuss the advances in the development of SIRT6 activators and elucidate their pharmacological profiles, which may provide novel treatment strategies for these skeletal diseases.展开更多
The biomechanical relationship between the articular cartilage defect and knee osteoarthritis (OA) has not been clearly defined. This study presents a 3D knee finite element model (FEM) to determine the effect of cart...The biomechanical relationship between the articular cartilage defect and knee osteoarthritis (OA) has not been clearly defined. This study presents a 3D knee finite element model (FEM) to determine the effect of cartilage defects on the stress distribution around the defect rim. The complete knee FEM, which includes bones, articular cartilages, menisci and ligaments, is developed from computed tomography and magnetic resonance images. This FEM then is validated and used to simulate femoral cartilage defects. Based on the obtained results, it is confirmed that the 3D knee FEM is reconstructed with high-fidelity level and can faithfully predict the knee contact behavior. Cartilage defects drastically affect the stress distribution on articular cartilages. When the defect size was smaller than 1.00cm2, the stress elevation and redistribution were found undistinguishable. However, significant stress elevation and redistribution were detected due to the large defect sizes ( 1.00cm2). This alteration of stress distribution has important implications relating to the progression of cartilage defect to OA in the human knee joint.展开更多
基金Supported by National Key R&D Program(2019YFC1712500)Science and Technology Program of Guizhou Province([2020]3003)Project of Guizhou University of Traditional Chinese Medicine(2018YFC170810520).
文摘[Objectives]To explore the protective effect and molecular mechanism of Shui People s Classic Prescription Jipei Dilong Ointment on knee osteoarthritis in rats.[Methods]72 SPF male SD rats were divided into control group,model group,Jipei Dilong Ointment high,medium and low dose groups,and positive drug Diclofenac group,with 12 rats in each group.Except the control group,all other groups were injected with 0.2 mL of 2%papain and 0.3%L-cysteine mixture into knee joint cavity to establish osteoarthritis model,while the control group was injected with the same amount of normal saline.The Lequesne MG score was used to determine the success of the model.After successful modeling,external administration was given for 4 weeks.The histopathological changes in articular cartilage and synovium were observed by HE staining;the levels of TNF-α,IL-1βand COX-2 in serum were detected by ELISA,and the relative expression of MMP-9 and TIMP-1 mRNA in cartilage was detected by qRT-PCR;the relative expression of MMP-9,TIMP-1,TLR4,MyD88 and NF-κB in rat cartilage was detected by Western-blot.[Results]Compared with the model group,Jipei Dilong Ointment could significantly reduce the Lequesne MG score and Mankin s score of arthritic rats(P<0.01);significantly improve the pathological changes in articular cartilage and synovium,reduce tissue edema,necrosis,inflammatory cell infiltration and fibrous tissue proliferation;reduce the expression of MMP-9 mRNA(P<0.01)in different degrees and increase the expression of TIMP-1 mRNA(P<0.01);reduce the relative expression of MMP-9,TLR4,MyD88 and NF-κB protein in different degrees(P<0.01),and significantly increase the relative expression of TIMP-1 protein in cartilage(P<0.01).[Conclusions]Jipei Dilong Ointment can improve the joint injury of osteoarthritis rats,and the mechanism may be related to the regulation of TLR4/MyD88/NF-κB signaling pathway and the ratio of MMP-9/TIMP-1.
文摘This study is designed to determine whether the outermost layer of articular cartilage is deficient in Osteoarthritis (OA). Phospholipids present in healthy and osteoarthritis (OA) synovial fluid show significant differences in their concentration. While examining the surface properties of OA joints, we found that OA PLs molecules cannot support lubrication, and increased friction was observed. Our lubrication mechanism was based on a surface active phospholipids (SAPL) multibilayer which in OA condition was deactivated and removed from the cartilage surface under OA conditions. Cartilage wettability study clearly demonstrated a significant decrease in hydrophobicity, the contact angle, θ (theta), dropping from 103° from bovine healthy cartilage to 65° in surface partially depleted and 35.1° for completely depleted surface. These results are discussed in the context that surface active phospholipid (SAPL) and lubricin, each has specific roles in a lamellar-repulsive lubrication system. However, deactivated phospholipid molecules are major indicator of cartilage wear (model) introduced in this study.
基金supported by grants from the State Key Program of National Natural Science of China (31630093)the National Natural Science Foundation of China (31571512, 31871476, and 81241062)+1 种基金the Beijing Nova Program (Z161100004916146)the National Basic Research Program of China (2012CB966904)
文摘Osteoarthritis(OA) is an age-related disorder that is strongly associated with chondrocyte senescence. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the underlying mechanism are unclear. In this study, we found activated Akt signaling in human OA cartilage as well as in a mouse OA model with surgical destabilization of the medial meniscus.Genetic mouse models mimicking sustained Akt signaling in articular chondrocytes via PTEN deficiency driven by either Col2a1-Cre or Col2a1-Cre^(ERT2) developed OA, whereas restriction of Akt signaling reversed the OA phenotypes in PTEN-deficient mice.Mechanistically, prolonged activation of Akt signaling caused an accumulation of reactive oxygen species and triggered chondrocyte senescence as well as a senescence-associated secretory phenotype, whereas chronic administration of the antioxidant N-acetylcysteine suppressed chondrocyte senescence and mitigated OA progression in PTEN-deficient mice. Therefore,inhibition of Akt signaling by PTEN is required for the maintenance of articular cartilage. Disrupted Akt signaling in articular chondrocytes triggers oxidative stress-induced chondrocyte senescence and causes OA.
基金Sponsored by the International Science and Technology Cooperation Project of China(Grant No.2009DFA32050)
文摘The sEMG signals are collected from the vastus lateralis,vastus medialis,biceps femoris,and semitendinosus of lower extremity during level walking among control subjects and knee osteoarthritis (OA) patients,the latter including mild,moderate and severe degree.The 5-fold cross-validation is used to measure the accuracy of the proposed analysis algorithm on collected sEMG recordings.For comparison,the more classical feature vectors of form factor,degree of skewness,kurtosis,and wavelet entropy are also tested.In experiment,the normalized energy ratio and marginal spectrum ratio achieve larger accuracy than the other features for all the four muscular groups.Moreover the accuracy of vastus medialis and biceps femoris are larger than that of vastus lateralis and semitendinosus.These results suggest that the normalized energy ratio and marginal spectrum ratio via the analysis of knee sEMG signals by HHT can server as characteristic parameters to easily classify osteoarthritis with noninvasive method.The more important muscular groups for maintaining the knee joint function are medialis and biceps femoris;as a result of that they should be exercise especially for rehabilitation.
基金Supported by the National Science and Technology Support Program of China(2012BAD46B02-03)
文摘The pathogenesis of equine Osteoarthritis(OA) is more complex, and the disease in the early stage is not easy to be found, therefore, the early diagnosis and treatment are very important. Based on this, this experiment established OA model induced by equine, aimed to study the changes of contents of Matrix Metalloproteinases-3(MMP-3), Matrix Metalloproteinases-13(MMP-13), Aggrecanase(ADAMTS-5), Hyaluronic Acid(HA) and Osteocalcin(OCN) in synovial fluid, and establish rapid diagnostic technique for the equine OA. Thirteen Mongolian equines were used in these induction studies. Equines were randomly divided into two groups: the experimental group contained eight equines and the control group contained five equines. The experimental group was to build the equine osteoarthritis model. The induction was done through Intra-articular(IA) injection of 2 m L Amphotericin-B in equines' left carpal joints. The equine of the control group was injected into 2 m L physiological saline in equines' left carpal joints. Synovial fluid was collected every week until the 9th week. The contents of MMP-3, MMP-13, ADAMTS-5, HA and OCN in synovial fluid were evaluated by using ELISA kits. Equine OA model, compared with the control group, starting from the 1st to the 2nd week after induction model, the content of MMP-3, MMP-13, ADAMTS-5, HA and OCN tended to increase, but there was no significant increase, from the 2nd to the 3rd week they significantly increased(p<0.05) and kept increasing trend until the 9th week. In OA model, MMP-3, MMP-13, ADAMTS-5, HA and OCN showed a rising trend in joint fluid, which would accelerate the cartilage, subchondral bone degradation and metabolism of these proteases increased, and ADAMTS-5 and HA in the early stage increased significantly.
基金The tribometer(UMT-3,Bruker,USA)setup was purchased thanks to the Grant No.91112026 from the Netherlands Organization for Health Research and Development(ZON-MW).Figure 8 is created with biorender.comWe also would like to thank China Scholarship Council for a four-year scholarship to Ph.D.candidate Ke REN(Grant No.CSC201806400039).
文摘Healthy cartilage is a water-filled super lubricious tissue.Collagen type II provides it structural stability,and proteoglycans absorb water to keep the cartilage in a swollen condition,providing it the ability to creep and provide weeping lubrication.Osteoarthritis(OA)is a degenerative and debilitating disorder of diarthrodial joints,where articular cartilage damage originates from enzymatic degradation and mechanical damage(wear).The objective of this research is to observe the level of cartilage damage present in knee arthroplasty patients and to understand the friction and creep behavior of enzymatically degraded bovine cartilage in vitro.Lateral(Lat)and medial(Med)condylar cartilages from OA patients undergoing total knee arthroplasty showed signs of enzymatic degradation and mechanical damage.Bovine cartilages were exposed to collagenase III and chondroitinase ABC to degrade collagen and proteoglycans,respectively.The loss of proteoglycans or collagen network and morphological changes were observed through histology and the atomic force microscope(AFM),respectively.A significant effect on creep due to enzymatic treatment was not observed.But the enzymatic treatment was found to significantly decrease the coefficient of friction(COF)at 4 N,while higher COF was shown from chondroitinase ABC degraded cartilage at 40 N.Collagenase III treatment leads to the release of intact proteoglycans at the sliding interface,while chondroitinase ABC treatment leads to the loss of chondroitin sulfate(CS)from the proteoglycans.Chondroitinase ABC-digested bovine cartilage mimicked patient samples the best because of the similar distributions of proteoglycans,collagen network,and friction behavior.
基金The experimental test rig was funded by Maof Fellowships,the Council for Higher Education of Israel(Prof.Haytam KASEM).
文摘Studying the lubrication properties of osteoarthritis(OA)synovial fluid(SF)enables an understanding of the boundary lubrication joint,mobility,and friction.However,tribology has never been combined with the clinical reality of the presence of worn particles within the synovial fluid and how they affect the osteoarthritic joints.Part of the problem relates to the tribology methods studying friction by applying inadequate pin-on-disc techniques.In this study,synovial fluid with and without worn particles was studied using a customized tribometer.This method enables opening the contact at the end of each cycle and simulates better contact conditions of a natural knee joint and can thus be applied for evaluating the severity of joint OA and the treatment given to the patient.
文摘The skeletal system is a dynamically balanced system, which undergoes continuous bone resorption and formation to maintain bone matrix homeostasis. As an important ADP-ribosylase and NAD+-dependent deacylase, SIRT6 (SIR2-like protein 6) is widely expressed on various kinds of bone cells, such as chondrocytes, osteoblasts, osteoclasts. The aberration of SIRT6 impairs gene expression (e.g., NF-κB and Wnt target genes) and cellular functions (e.g., DNA repair, glucose and lipid metabolism, telomeric maintenance), which disturbs the dynamic balance and ultimately leads to several bone-related diseases. In this review, we summarize the critical roles of SIRT6 in the onset and progression of bone-related diseases including osteoporosis, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, as well as the relevant signaling pathways. In addition, we discuss the advances in the development of SIRT6 activators and elucidate their pharmacological profiles, which may provide novel treatment strategies for these skeletal diseases.
基金the National Natural Science Foundation of China (No. 81071235)the Medicine and Engineering Interdisciplinary Fund of Shanghai Jiaotong University (No. YG2010MS26)
文摘The biomechanical relationship between the articular cartilage defect and knee osteoarthritis (OA) has not been clearly defined. This study presents a 3D knee finite element model (FEM) to determine the effect of cartilage defects on the stress distribution around the defect rim. The complete knee FEM, which includes bones, articular cartilages, menisci and ligaments, is developed from computed tomography and magnetic resonance images. This FEM then is validated and used to simulate femoral cartilage defects. Based on the obtained results, it is confirmed that the 3D knee FEM is reconstructed with high-fidelity level and can faithfully predict the knee contact behavior. Cartilage defects drastically affect the stress distribution on articular cartilages. When the defect size was smaller than 1.00cm2, the stress elevation and redistribution were found undistinguishable. However, significant stress elevation and redistribution were detected due to the large defect sizes ( 1.00cm2). This alteration of stress distribution has important implications relating to the progression of cartilage defect to OA in the human knee joint.
