Abstract
Osteoarthritis (OA) is a progressive degenerative joint disorder with cartilage degradation as the primary cause of joint pain and loss of joint function. B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) is a key regulator of apoptosis and serves as a signal transducer of the NFκB and Hif-1α pathways, both of which are involved in osteoarthritic cartilage degradation. However, whether BCLAF1 contributes to the pathogenesis of OA remains unclear. The present study aims to elucidate the role of BCLAF1 in osteoarthritic cartilage degradation and the underlying mechanisms. We found that BCLAF1 levels were increased in cartilage tissue from OA patients, elder and surgery-induced OA mice, and primary chondrocytes treated with inflammatory cytokines. Knockdown of Bclaf1 in chondrocytes inhibited the expression of catabolic factors and apoptosis rate, while promoting the expression of anabolic factors and enhancing chondrocyte functions such as viability and migration. Conversely, overexpression of Bclaf1 produced the opposite effects. Furthermore, intra-articular injection of adenovirus containing shRNA targeting Bclaf1 attenuated cartilage degradation and osteophytosis in a mouse OA model, while overexpression of BCLAF1 further aggravated cartilage degradation and osteophytosis in vivo. Through immunoprecipitation and protein mass spectrometry, we identified LAMTOR2 as a key mediator of BCLAF1 by regulating the translocation of BCLAF1 into the nucleus. Our findings reveal the critical role and key mechanisms of BCLAF1 in regulating cartilage degradation, representing a novel molecular target for the therapeutic development of OA.