OSTF1 knockdown mitigates IL-1β-induced chondrocyte injury via inhibiting the NF-κB signaling pathway

Osteoarthritis (OA) is an age-related joint disease characterized by progressive heterogeneous changes in articular cartilage and subchondral bone. Osteoclast stimulating factor 1 (OSTF1) is a small intracellular protein involved in bone formation and bone resorption. However, to our best knowledge, its role in OA is still unclear. In this study, an OA rat model was established by anterior cruciate ligament transection (ALCT). OSTF1 was increased in the cartilage tissues of OA patients and OA rats. Next, the role of OSTF1 in interleukin-1 beta (IL-1 beta)-induced chondrocyte apoptosis, inflammation and extracellular matrix degradation was explored through loss of function assays. Strikingly, OSTF1 knockdown relieved IL-1 beta-induced chondrocyte apoptosis, with decreased cleaved caspase-3 and cleaved PARP levels. Besides, OSTF1 knockdown restrained IL-1 beta-induced inflammation and degradation of extracellular matrix of chondrocytes. Subsequently, the molecular mechanism of OSTF1 was explored. Transcriptomic analysis revealed the potential gene network map regulated by OSTF1 knockdown. Some differentially expressed genes (DEGs) were involved in regulating the NF-kappa B signaling pathway. Furthermore, our results demonstrated that OSTF1 knockdown inhibited IL-1 beta-activated the NF-kappa B signaling pathway. Ultimately, we analyzed the potential gene network map regulated by OSTF1 and its downstream NF-kappa B. Bioinformatics analysis showed that 18 DEGs in OSTF1-silenced chondrocytes overlapped with the NF-kappa B downstream targets. Collectively, our findings indicate that OSTF1 knockdown mitigates IL-1 beta-induced chondrocyte injury via inhibiting the NF-kappa B signaling pathway.