Kartogenin mediates cartilage regeneration via stimulating the IL-6/Stat3-dependent proliferation of cartilage stem/progenitor cells

Abstract

Background: Declination of endogenous stem cells in cartilage is regarded as the cause of cartilage degeneration. Kartogenin (KGN) is well known to play an important role in chondrogenesis of mesenchymal stem cells (MSC).Methods: Using MSCs isolated from rat cartilages, we analyzed the changing of transcriptomics after the treatment of KGN in vitro. DMM animal models were then applied to identified the effect of MSCs proliferation in vivo after KGN capsule injection. Furthermore, we explored the potential mechanisms how KGN mediates cartilage regeneration and proliferation of cartilage progenitor cells.Results: In this study, we demonstrate that KGN can promote the proliferation of MSC from cartilage, respectively. The percentage of G2-M phase cells in culture reached over 10%, nearly twice as the control group with KGN treatment. Transcriptomic profiling of rat cartilage stem/progenitor cells (CSPC) revealed that the expression of at least 20 cell cycle related genes was significantly changed in response to the KGN treatment. IL-6 and its co-receptor Gp130 gene expression level are much higher than the untreated control. The phosphorylation of the IL-6-downstreamt molecular Stat-3 was enhanced upon the KGN stimulation. The knee joint injury animal model further showed the increased articular cartilage thickness after KGN treatment. Interestingly, the IHC staining also demonstrated the up-regulated level of Stat-3 phosphorylation and enhanced distribution of CD44+/CD105+ cells in the KGN-treated cartilage.Conclusion: Taken together, our data suggest that KGN promotes cartilage regeneration at least partially by stimulating the IL-6/Stat3-dependent proliferation of stem cells resident in the cartilage.