Kartogenin Promotes the BMSCs Chondrogenic Differentiation in Osteoarthritis by Down-Regulation of miR-145-5p Targeting Smad4 Pathway

Transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for cartilage degeneration of osteoarthritis (OA). But controlling chondrogenic differentiation of the implanted MSCs in the joints remains a challenge. The role of kartogenin (KGN) for chondrogenesis of MSCs has been widely reported, however, the mechanism of chondrogenesis has not been elucidated in OA. In this study, we investigated the miR-145-5p, TGF-β, Samd4, and p-stat3/stat3 expression in cartilage of OA patients and bone marrow mesenchymal stem cells (BMSCs) treated with KGN or miR-145-5p inhibitor. In addition, the cell proliferation and chondrogenic differentiation in vitro and in vivo of BMSCs treated with KGN was also detected. In OA patients, the expression of miR-145-5p was up-regulated, and the expression of TGF-β, Samd4, and p-stat3/stat3 was inhibited. When the BMSCs treated with miR-145-5p inhibitor, the expression of TGF-β, Samd4, and p-stat3/stat3 was also significantly up-regulated. KGN-treated BMSCs had better proliferation and chondrogenic differentiation by up-regulating the expression of Sox 9, Col-2a1, aggrecan in vitro and in OA by down-regulation of miR-145-5p targeting Smad4 pathway. Moreover, intra-articular injection of KGN-treated BMSCs had a better pain relief effect in OA. The double effect on cartilage protection and pain relief indicates a great potential of intra-articular injection of KGN-treated BMSCs for the treatment of OA.