Research Of Cyclic Committed Stress-induced Scinderin Regulates Progress Of Developmental Dysplasia Of The Hip

Background: Developmental dysplasia of the hip(DDH)is a congenital and developmental hip disease with high incidence.As the incompatibility between acetabulum and femoral head,patients always have early osteoarthritis(OA)performance,which puts a heavy burden on the community and individuals.Objective: To study the specific regulatory mechanism of Scinderin(SCIN)in the process of DDH to OA,with cartilage degeneration and osteophyte formation.Methods: Detecting the expression of SCIN in articular cartilage of DDH patients and rats.Analyzing the underlying mechanism in cartilage degeneration with application of cyclic Committed Stress in vitro.Studying the expression and functional mechanism of SCIN during the process of osteoblast and osteoclast differentiation induced by bone marrow mesenchymal stem cells and bone marrow macrophage.In addition,constructing femoral defect of nude mice to observe new bone formation.Results: The expression of SCIN in articular cartilage of hip joint was increased in DDH patients and DDH model rats.Stress imbalance can lead to cartilage degeneration,and in this process SCIN protein levels increased,in addition,NF-?B P65 pathway was activated by the application of NF-?B pathway inhibitor BAY-11-7082,we observed that chondrocyte degeneration phenotype was rescued,meanwhile,by transfection of after si-SCIN,we got a similar result.We assessed the expression of SCIN increased during osteogenic and osteoclasticconditions under cyclic stress loading.When using lentiviral vector to overexpress SCIN,both osteoblasts and osteoblasts were enhanced.Furthermore,Smad1 / 5/8,MAPK P38 and NF-?B pathway were activated during osteogenesis-osteoclastogenesis induction.In order to further verify the effect of SCIN on osteogenesis and osteoclast formation,we constructed a model of nude mice femoral defect.By injecting matrix gel containing SCIN-overexpression mesenchymal stem cells,Micro-CT analysis was used to compare with control group and overexpression of SCIN group,new bone formation increased significantly in the latter group.Conclusion:(1)SCIN regulates cartilage degeneration in DDH through NF-?B P65 pathway under the condition of cyclic stress.(2)SCIN modulates osteogenesis-osteoclastogenesis stabilization through Smad1 / 5/8,MAPK P38 and NF-?B pathway,leading to the formation of osteophyte with the role of cyclic stress.