Abstract
BackgroundAnterior cruciate ligament (ACL) injury is recognized as a risk factor for osteoarthritis (OA) progression. Herein, the function of TAF15 in ACL injury-induced OA was investigated. MethodsOA cell model and OA mouse model were established by interleukin-1 beta (IL-1β) stimulation and ACL transection administration, respectively. The pathological changes were analyzed by histopathology. The mRNA and protein expressions were assessed using qRT-PCR, Western blot and IHC. Chondrocyte viability and apoptosis were examined by CCK8 assay and TUNEL staining, respectively. The interactions between TAF15, BRD4 and GREM1 were analyzed by RIP or ChIP assay. ResultsTAF15 expression was markedly elevated in OA, and its knockdown suppressed IL-1β-induced chondrocyte apoptosis and ECM degradation in vivo and cartilage pathological changes in vitro. TAF15 promoted BRD4 mRNA stability, and TAF15 silencing's repression on chondrocyte apoptosis and ECM degradation induced by IL-1β was abrogated following BRD4 overexpression. BRD4 promoted GREM1 expression by directly binding with GREM1. In addition, the GREM1/NF-κB pathway functioned as the downstream pathway of BRD4 in promoting OA progression. ConclusionTAF15 upregulation facilitated chondrocyte apoptosis and ECM degradation during OA development by acting on the BRD4/GREM1/NF-κB axis, which provided a theoretical basis for the development of novel therapies for OA.
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