Abstract
Synovial fluid-derived mesenchymal stem cells (SF-MSCs) represent a superior source of stem cells and have great potential for autologous transplantation for cartilage regeneration. Transforming growth factor-β3 (TGF-β3) has been demonstrated to stimulate the chondrogenic differentiation of MSCs. Recently, the small molecule kartogenin (KGN) was reported to enhance chondrogenic differentiation and cartilage regeneration. The effects of KGN and TGF-β3 on the in vitro chondrogenic differentiation of rabbit SF-MSCs were studied. The monolayer and pellet cultures of rabbit SF-MSCs were stimulated in vitro using either KGN or TGF-β3 alone or in combination for 21 days. The in vivo therapeutic effects of KGN combined with TGF-β3 were studied using an intra-articular delivery of autologous rabbit SF-MSCs to cartilage defects in a rabbit model. Compared to a single treatment, the in vitro results demonstrated that the combination of KGN and TGF-β3 resulted in significantly increased protein expression levels of type II collagen (COL II) and SRY-box 9 (SOX9) and decreased the expression level of type X collagen (COL X). Compared with the regenerated cartilage in the single treatment groups, the intra-articular injection of rabbit SF-MSCs mixed with TGF-β3 and KGN exhibited substantial amounts of regenerated cartilage in the defective areas in the medial femoral condyles. We noted that the thicker, hyaline-like cartilaginous tissue contained abundant levels of extracellular matrix, which is characteristic of cartilage. This study demonstrated that TGF-β3 and KGN exhibit synergistic effects for the promotion of the chondrogenesis of rabbit SF-MSCs and can effectively repair cartilage defects through the regeneration of hyaline cartilage.