Journal
SCIENCE
Volume 336, Issue 6082, Pages 717-721Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1215157
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Funding
- California Institute for Regenerative Medicine [TR2-01829]
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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.
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