Osteoarthritis(OA),long considered a primary disorder of articular cartilage,is commonly associated with subchondral bone sclerosis.However,the cellular mechanisms responsible for changes to subchondral bone in OA,and...Osteoarthritis(OA),long considered a primary disorder of articular cartilage,is commonly associated with subchondral bone sclerosis.However,the cellular mechanisms responsible for changes to subchondral bone in OA,and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration,remain unclear.In knee joints from human patients with end-stage OA,we found evidence of profound defects in osteocyte function.Suppression of osteocyte perilacunar/canalicular remodeling(PLR)was most severe in the medial compartment of OA subchondral bone,with lower protease expression,diminished canalicular networks,and disorganized and hypermineralized extracellular matrix.As a step toward evaluating the causality of PLR suppression in OA,we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact,using Cre recombinase driven by the 9.6-kb DMP1 promoter.Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone,but it also compromised cartilage.Even in the absence of injury,osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content,change chondrocyte production of collagen II,aggrecan,and MMP13,and increase the incidence of cartilage lesions,consistent with early OA.Thus,in humans and mice,defects in PLR coincide with cartilage defects.Osteocyte-derived MMP13 emerges as a critical regulator of cartilage homeostasis,likely via its effects on PLR.Together,these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis.展开更多
Objective:To observe the differences in clinical effect on knee osteoarthritis(KOA)between the holistic stratification acupotomy and the joint injection with sodium hyaluronate so as to provide a safe and effective tr...Objective:To observe the differences in clinical effect on knee osteoarthritis(KOA)between the holistic stratification acupotomy and the joint injection with sodium hyaluronate so as to provide a safe and effective treatment for KOA.Methods:A total of 100 KOA patients were randomly divided into an acupotomy group and a sodium hyaluronate group,50 patients in each one.In the acupotomy group,the holistic stratification acupotomy was adopted.In the sodium hyaluronate group,sodium hyaluronate injection was applied in the joints.The index of Western Ontario and McMaster University(WOMAC)and the expressions of MMP1 and MMP13 in bursal fluid of the patients were compared before and after treatment in the patients between two groups before and after treatment,and the clinical therapeutic effect was observed.Results:After treatment,WOMAC score of each dimension and the concentrations of MMP1 and MMP13 in bursal fluid of the patients of either group were all lower than those before treatment(all P<0.05).After treatment,WOMAC score of each dimension and the concentrations of MMP1 and MMP13 in bursal fluid in the acupotomy group were lower than the sodium hyaluronate group(all P<0.05).The total effective rate in the acupotomy group was higher than that of the sodium hyaluronate group(P<0.05).Conclusion:Both the holistic stratification acupotomy and the joint injection with sodium hyaluronate are effective on KOA in this trial.However,the therapeutic effect of holistic stratification acupotomy is remarkable,which is probably related to the improvements in inflammatory response.展开更多
基金supported by the National Institute of Dental and Craniofacial Research (R01 DE019284)the Department of Defense (OR130191)+1 种基金the Read Research Foundation, the National Science Foundation (GRFP 1650113 and CDMI)the National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30 AR06626201)
文摘Osteoarthritis(OA),long considered a primary disorder of articular cartilage,is commonly associated with subchondral bone sclerosis.However,the cellular mechanisms responsible for changes to subchondral bone in OA,and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration,remain unclear.In knee joints from human patients with end-stage OA,we found evidence of profound defects in osteocyte function.Suppression of osteocyte perilacunar/canalicular remodeling(PLR)was most severe in the medial compartment of OA subchondral bone,with lower protease expression,diminished canalicular networks,and disorganized and hypermineralized extracellular matrix.As a step toward evaluating the causality of PLR suppression in OA,we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact,using Cre recombinase driven by the 9.6-kb DMP1 promoter.Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone,but it also compromised cartilage.Even in the absence of injury,osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content,change chondrocyte production of collagen II,aggrecan,and MMP13,and increase the incidence of cartilage lesions,consistent with early OA.Thus,in humans and mice,defects in PLR coincide with cartilage defects.Osteocyte-derived MMP13 emerges as a critical regulator of cartilage homeostasis,likely via its effects on PLR.Together,these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis.
基金Supported by Youth Science Foundation of National Natural Science Foundation of China:81,704,195Research Project of Integrated Traditional Chinese and Western Medicine of Tianjin Health Commission:015,018。
文摘Objective:To observe the differences in clinical effect on knee osteoarthritis(KOA)between the holistic stratification acupotomy and the joint injection with sodium hyaluronate so as to provide a safe and effective treatment for KOA.Methods:A total of 100 KOA patients were randomly divided into an acupotomy group and a sodium hyaluronate group,50 patients in each one.In the acupotomy group,the holistic stratification acupotomy was adopted.In the sodium hyaluronate group,sodium hyaluronate injection was applied in the joints.The index of Western Ontario and McMaster University(WOMAC)and the expressions of MMP1 and MMP13 in bursal fluid of the patients were compared before and after treatment in the patients between two groups before and after treatment,and the clinical therapeutic effect was observed.Results:After treatment,WOMAC score of each dimension and the concentrations of MMP1 and MMP13 in bursal fluid of the patients of either group were all lower than those before treatment(all P<0.05).After treatment,WOMAC score of each dimension and the concentrations of MMP1 and MMP13 in bursal fluid in the acupotomy group were lower than the sodium hyaluronate group(all P<0.05).The total effective rate in the acupotomy group was higher than that of the sodium hyaluronate group(P<0.05).Conclusion:Both the holistic stratification acupotomy and the joint injection with sodium hyaluronate are effective on KOA in this trial.However,the therapeutic effect of holistic stratification acupotomy is remarkable,which is probably related to the improvements in inflammatory response.
