Positive Feedback Regulations Between USP15 And ERK2 Promote Cartilage Repair In Experimental Osteoarthritis

Objective:Osteoarthritis(OA)is characterized by progressive loss of articular cartilage.The activation of the TGFβ/Smad signaling pathway can reduce the degradation of cartilage tissue mediated by inflammatory cytokines.It is of great significance in slowing down cartilage loss in the pathological process of OA.Studies have shown that USP15 can enhance TGFβ/Smad signaling by stabilizing TβR-I and increasing p-smad protein levels.ERK2 is an important molecule in the non-classical Smad pathway.When it is activated,it also can promote the TGFβ/Smad signaling transduction.The purpose of this study was to explore the correlation between ERK2 and USP15 in TGFβ/Smad signaling pathway,as well as specific mechanisms and roles of them in the repair of osteoarthritic cartilage.Methods:1.The role of USP15 and ERK2 in the cartilage repair of osteoarthritis was explored by western blotting,Crispr technology,protein overexpression,immunofluorescence,rat osteoarthritis model,immunohistochemistry,Safranin-O fast green staining,OARSI score,real-time quantitative PCR and so on.2.Further study on the regulation between USP15 and ERK2 were found by western blotting,Crispr technology,protein overexpression,immunoprecipitation,immunofluorescence co-localization,nucleo-plasma separation technology,immunohistochemistry and so on.Results:1.ERK2 can regulate TGFβ/Smad signaling pathway by increasing USP15 and ultimately affect the repair of osteoarthritic cartilage.2.ERK2 can form a complex with USP15 and then be deubiquitinated,which is followed by activation and translocation.Conclusion:Taken together,our study revealed a positive feedback regulation between USP15 and ERK2,which plays a critical role in the interaction of SMAD and non-SMAD signaling pathways to promote cartilage repair in experimental OA.