The cartilage damage that is characteristic of osteoarthritis might be repaired using compounds that promote the differentiation of multipotent mesenchymal stem cells into chondrocytes. Using a high-throughput screen, Johnson et al. identified kartogenin as such a molecule. In models of osteoarthritis, the compound (given at early stages of the disease) promoted regeneration of cartilage and alleviated pain. Mechanistic studies showed that kartogenin binds to the actin binding protein filamin A, disrupts its interaction with the transcription factor CBFβ (core binding factor subunit β) and induces chondrogenesis by regulating the CBFβ–RUNX1 (runt-related transcription factor 1) transcriptional programme.
ORIGINAL RESEARCH PAPER
Johnson, K. et al. A stem-cell based approach to cartilage repair. Science 336, 717–721 (2012)Article
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Harrison, C. Repairing cartilage in osteoarthritis. Nat Rev Drug Discov 11, 442 (2012). https://doi.org/10.1038/nrd3763
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DOI: https://doi.org/10.1038/nrd3763