Introduction:Kartogenin (KGN) is a small-molecule compound that has been reported to improve the chondrogenic differentiation of mesenchymal stem cellsin vitroand to alleviate knee joint osteoarthritis in animal models. However, whether KGN has any effect on temporomandibular joint osteoarthritis (TMJOA) remains unclear.Methods:We first performed partial temporomandibular joint (TMJ) discectomy to induce TMJOA in rats. Histological analysis, tartrate-resistant acid phosphatase staining, and immunohistochemistry were used to assess the therapeutic effect of KGN on TMJOAin vivo. CCK8 and pellet cultures were used to determine whether KGN treatment could promote the proliferation and differentiation of FCSCs in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of aggrecan, Col2a1, and Sox9 in FCSCs. Furthermore, we performed western blot to analysis the effect of KGN treatment on the expression of Sox9 and Runx2 in FCSCs.Results and discussion:Histological analysis, tartrate-resistant acid phosphatase staining, and immunohistochemistry showed that intra-articular injection of KGN attenuated cartilage degeneration and subchondral bone resorption in vivo. Further analyses of the underlying mechanisms revealed that KGN enhanced chondrocyte proliferation, increased the number of cells in both superficial and proliferative zones of TMJ condylar cartilagein vivo, enhanced the proliferation and chondrogenic differentiation of fibrocartilage stem cells (FCSCs), and upregulated the expression of chondrogenesis-related factorsin vitro. Collectively, in our study, KGN was shown to promote FCSC chondrogenesis and restore TMJ cartilage, suggesting that KGN injections might be a potential treatment for TMJOA.