软骨发生
骨关节炎
间充质干细胞
细胞生物学
软骨
软骨细胞
转录因子
干细胞
运行x1
化学
癌症研究
生物
医学
解剖
病理
生物化学
基因
造血
替代医学
标识
DOI:10.1016/j.joca.2013.02.019
摘要
Osteoarthritis (OA) is a degenerative joint disease that involves destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multi-potent mesenchymal stem cells (MSCs) in to chondrocytes may stimulate the repair of damaged cartilage. Using an image-based, high throughput screen we identified the small molecule kartogenin, which promotes selective chondrocytes differentiation (EC50 = 100 nM), shows chondro-protective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A (FLNA), disrupts its interaction with the transcription factor CBFβ and induces chondrogenesis by regulating the CBFβ-RUNX1 transcriptional program. This work provides new insight into the control of chondrogenesis that may ultimately lead to a stem-cell based therapy for osteoarthritis.
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