Science：小分子可刺激小鼠软骨再生

4月5日，国际著名杂志Science在线刊登的一项新的研究报告中称，一种叫做kartogenin的小分子可在小鼠中刺激软骨的再生。这些发现提示，该分子可以成为一种针对骨关节炎的新的以药物为基础的疗法；骨关节炎是一种以慢性关节疼痛和能力丧失为特征的普遍的退行性关节疾病。位于健康和有病关节中的间充质干细胞是多能成体干细胞，它们有分化成为各种细胞类型的能力，人们怀疑其参与软骨的修复。

Kristen Johnson及其同事们对间充质干细胞进行了一个化学筛检并发现一个叫做kartogenin的小分子，它可通过诱使间充质干细胞转变成为软骨细胞（该细胞在软骨中被发现）而促进软骨的产生。

当给有骨关节炎样症状的小鼠局部施予kartogenin可触发其体内的软骨的发育。该分子是通过中断被称为细丝蛋白A和CBF beta这两个蛋白之间的相互作用而起作用的，而其结果是该分子控制了在肌肉骨骼发育中起到关键性作用的一个蛋白家族的表达。（生物谷Bioon.com）

doi:10.1126/science.1215157
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A Stem Cell–Based Approach to Cartilage Repair

Kristen Johnson1,*,†, Shoutian Zhu2,†, Matthew S. Tremblay1,2, Joshua N. Payette2, Jianing Wang2, Laure C. Bouchez2, Shelly Meeusen1, Alana Althage1, Charles Y. Cho1, Xu Wu3, Peter G. Schultz2,*

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 multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage. Using an image-based, high-throughput screen, we identified the small molecule kartogenin, which promotes chondrocyte differentiation (EC50 = 100 nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A, disrupts its interaction with the transcription factor CBFβ, and induces chondrogenesis by regulating the CBFβ-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell–based therapy for osteoarthritis.