A stem cell-based approach to cartilage repair

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.