Kartogenin (KGN) is a small molecule that promotes the selective differentiation of mesenchymal stem cells into chondrocytes, and thus, KGN stimulates cartilage regeneration. KGN also possess chondro-protective effect. Kartogenin (100 nM; 72 h) induces chondrocyte nodule formation in primary hMSCs. Kartogenin (10 nM-10 μM; 72 h) increases chondrocyte-specific gene expression in hMSCs. Kartogenin (0.12-10 μM; 48 h) inhibits nitric oxide (NO) and glycosaminoglycan (GAG) release induced by cytokines in primary bovine articular chondrocytes. Kartogenin (10 μM in 4μL of saline; i.a. on days 7 and 21) promotes cartilag erepair in collagenase VII-induced OA models in mice[3]. Kartogenin binds filamin A, disrupts its interaction with the transcription factor core-binding factor β subunit (CBFβ), and induces chondrogenesis by regulating the CBFβ-RUNX1 transcriptional program[4]. The DMM (destabilization of the medial meniscus) animal model showed increased articular cartilage thickness after IA (intra-articular) KGN injection. IHC staining also demonstrated upregulation of Stat3 phosphorylation and enhanced distribution of CD44+/CD105+ cells in cartilage following IA KGN injection[5]. KGN preconditioning likely improves the chondrogenic differentiation of hUCMSCs (human umbilical cord MSCs) by committing them to a precartilaginous stage with enhanced JNK phosphorylation and suppressed β-catenin[6].
搜索
