The SDFL1/CXCR4 Axis Coordinates The Crosstalk Between Subchondral Bone And Articular Cartilage During Osteoarthritis Pathogenesis

Objective.The crosstalk between subchondral bone and overlying cartilage is a central feature of Osteoarthritis(OA).Recent evidences have attracted more attention towards the role of SDF-1/CXCR4 axis on OA development.We aimed to examine whether and how SDF-1/CXCR4 axis modulates the crosstalk between subchondral bone and articular cartilage during OA pathogenesis.Methods.We purchased 3-month-old male C57BL/6J mice and SD rats.OA model was induced by transection of the anterior cruciate ligament.Local administration of drug was achieved via osmotic infusion pump,which was implanted in tibial subchondral bone directly to insure drug delivery quantitative,continuous and steady over the entire course of the experiment.Results.We revealed that SDF-1/CXCR4 axis coordinated the crosstalk between subchondral bone and articular cartilage during OA progression.Firstly,SDF-1 induced subchondral bone deterioration by erroneous Mesenchymal Stem Cells(MSCs)recruitment and excessive bone resorption.Subchondral bone deterioration contributed to the traverse of SDF-1 from subchondral bone to overlying cartilage.Then,SDF-1 combined with CXCR4 in chondrocytes to induce articular cartilage degradation by promoting the shift of transforming growth factor-? receptor type I(TpRI)expression in chondrocytes from ALK5 to ALK1.More importantly,specific inhibition of SDF-1/CXCR4 axis attenuated OA by stabilizing subchondral bone microarchitecture,reducing SDF-1 in cartilage and abrogating the shift of T[pRI expression in chondrocytes.Conclusion.The SDF-1/CXCR4 axis couples subchondral bone deterioration and articular cartilage degeneration in OA pathogenesis.Specific inhibition of SDF-1/CXCR4 axis in subchondral bone or intervention of SDF-1 traverse may be therapeutic targets for OA.