The Mechanlsm Of BIP5 In Promoting Chondrocyte Senescence And Apoptosis In Osteoarthritis

BackgroundOsteoarthritis(osteoarthritis,OA)is the most common chronic degenerative disease.It can affect multiple parts of the body and occurs in the knee joint.It is often accompanied by joint pain,decreased mobility,and joint deformity.OA has always been a research hotspot,but no effective target has yet been found for treatment.Accumulated evidences showing that BMP5 is related to OA,but the specific mechanism of action is still unclear.A large number of studies have proved that BMP5 is related to OA,but its specific mechanism of action is still unclear.ObjectiveIn this study,we should clarify the expression of BMP5 in OA articular cartilage tissue,further explore the impact of chondrocyte BMP5 expression on the metabolic changes of chondrocytes in the course of OA,and finally determine the role,in which osteoarthritis,articular chondrocytes appear senescence and apoptosis.And to clarify the relationship between BMP5 and ERK/p38 MAPK signaling pathway in osteoarthritis progress and its molecular mechanism,for providing new potential targets for the prevention and treatment of osteoarthritis.MethodCollect articular cartilage specimens from normal OA patients,normal articular cartilage specimens,and their joint fluids to detect the expression of BMP5 in osteoarthritis by immunohistochemistry,western blot,and ELISA experiments.At the same time.c57/BL6 mice were used to construct DMM-OA osteoarthritis models and old models.The expression of BMP5 in knee cartilage was detected by IHC at 2 and 4 weeks after surgery.ATDC5 cells were used for siRNA transfection in vitro to knock out BMP 5,and the knockout effect was confirmed by real-time fluorescence quantitative(RT-qPCR)and western blot experiments.Chondrocytes stimulated with IL-1β,BMP5 was knocked out at the same time,exam the effect on Catabolic Synthesis of Chondrocytes.A mouse DMM-OA model was constructed,and BMP5 in chondrocytes was knocked out by injection of lentivirus into the articular cavity.The effects of knocking out BMP5 on arthritis in in vivo experiments were observed.By inducing chondrocyte senescence and apoptosis in vitro,the effects of knocking out BMP5 on chondrocyte senescence and apoptosis were observed.Recombinant protein BMP5(rhBMP5)and ERK inhibitor PD98059 were added to chondrocytes,and the effect of BMP5 on ERK/p38 MAPK signaling pathway was observed.ResultsBMP5 has a close relationship with OA.The expression of BMP5 in articular cartilage in OA patients and mice with osteoarthritis and old models was significantly higher than that in the normal group,and the expression in serum of OA patients was also significantly increased.Knockout of BMP5 in chondrocytes in vitro can down-regulate the expression of catabolism such as MMP13,ADAMTS5,IL-1,and up-regulate the expression of COL2A and ACAN anabolic.By injecting lentivirus through the knee joint,the degree of articular cartilage in the BMP5(DMM+LV-BMP5)knockout group was more complete than in the control group NC(DMM+LV-NC)group.The dyeing is deeper and more pigmented.In chondrocyte senescence and apoptosis induced by IL-1β and DMM-OA,knocking out BMP5 can down-regulate β-galactosidase staining,p16,p21,TUNEL staining,and cleaved-capse3 expression to relieve osteoarthritis Appears in cell senescence and apoptosis.Adding rhBMP5 to chondrocytes can activate the ERK/p38 MAPK signaling pathway,and adding PD98059 can reverse this phenomenon.ConclusionDuring the progression of OA,chondrocyte BMP5 expression is up-regulated,which can promote osteoarthritis by promoting chondrocyte catabolism,chondrocyte senescence,and apoptosis.Drugs that inhibit the activation of ERK1/2 signaling pathway of chondrocytes are potential targets for preventing and treating OA.