A Stem Cell–Based Approach to Cartilage Repair

• DOI: 10.1126/science.1215157
• Publication Date: 2012-04-06T04:07:27Z
• Authors: Kristen Johnson; Shoutian Zhu; Matthew S. Tremblay; Joshua N. Payette; Jianing Wang; Laure C. Bouchez; Shelly Meeusen; Alana Althage; Charles Y. Cho; Xu Wu; Peter G. Schultz
• Keywords: Cartilage, Articular; Cell Nucleus; 0303 health sciences; Filamins; Microfilament Proteins; Phthalic Acids; Mesenchymal Stem Cells; Core Binding Factor beta Subunit; High-Throughput Screening Assays; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; Chondrocytes; Contractile Proteins; Core Binding Factor Alpha 2 Subunit; Osteoarthritis; Animals; Humans; Regeneration; Anilides; Cattle; Chondrogenesis

Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules promote selective differentiation multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate repair damaged cartilage. Using an image-based high-throughput screen, we identified small molecule kartogenin, which promotes chondrocyte (median effective concentration = 100 nM), shows chondroprotective effects in vitro, efficacious two OA animal models. Kartogenin binds filamin A, disrupts its interaction with transcription factor core-binding β subunit (CBFβ), induces chondrogenesis by regulating CBFβ-RUNX1 transcriptional program. This work provides new insights control ultimately lead cell-based therapy for osteoarthritis.