A Stem Cell-Based Approach to Cartilage Repair
A Stem Cell-Based Approach to Cartilage Repair
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DOI：
10.1126/science.1215157
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发表时间：
2012-05-11
期刊：
影响因子：
56.9
通讯作者：
Schultz, Peter G.
中科院分区：
文献类型：
--
作者：
Johnson, Kristen;Zhu, Shoutian;Schultz, Peter G.
骨关节炎（OA）是一种退行性关节疾病，涉及关节软骨的破坏，并最终导致残疾。促进多能间充质干细胞（MSC）选择性分化为软骨细胞的分子可能刺激受损软骨的修复。使用基于图像的高通量筛选，我们鉴定了小分子kartogenin，其促进软骨细胞分化（中值有效浓度= 100 nM），在体外显示软骨保护作用，并且在两种OA动物模型中有效。Kartogenin结合细丝蛋白A，破坏其与转录因子核心结合因子β亚基（CBF β）的相互作用，并通过调节CBF β-RUNX 1转录程序诱导软骨形成。这项工作为控制软骨形成提供了新的见解，最终可能导致骨关节炎的干细胞治疗。
Osteoarthritis (OA) is a degenerative joint disease that involves the 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 (median effective concentration = 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 core-binding factor beta subunit (CBF beta), and induces chondrogenesis by regulating the CBF beta-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.