Transcriptomics

Dataset Information

3

A Chondrogenic Molecule that Repairs Cartilage by Transcriptional Regulation of CBF-beta


ABSTRACT: Osteoarthritis (OA) is a degenerative joint disease that involves destruction of articular cartilage and eventually leads to disability. Mesenchymal stem cells (MSCs) reside in healthy and diseased cartilage, and through their chondrogenic potential may provide a strategy for cartilage repair. To this end, we performed an image-based, high throughput screen and identified the small molecule, kartogenin, that promotes selective MSC differentiation into chondrocytes (EC50=100nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A and induces chondrogenesis by regulating the CBFbeta-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to an effective stem-cell based therapy for osteoarthritis. one compound, three doses, two time points, a vehicle control

ORGANISM(S): Homo sapiens  

SUBMITTER: Shelly Meeusen   Charles Y Cho  Jianing Wang  Matthew S Tremblay  Peter G Schultz  John R Walker  Joshua N Payette  Xu Wu  Alana Althage  Laure C Bouchez  Shoutian Zhu  Kristen A Johnson 

PROVIDER: E-GEOD-35546 | ArrayExpress | 2012-05-01

SECONDARY ACCESSION(S): GSE35546PRJNA152279

REPOSITORIES: GEO, ArrayExpress

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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 chondroprotect  ...[more]

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