Beta-catenin, cartilage, and osteoarthritis.
The early cellular events during the development of osteoarthritis (OA) are accelerated articular chondrocyte maturation and extracellular matrix degradation, which are usually seen in the weight-bearing region of articular cartilage. The results of our recent studies from transgenic OA mouse models indicate that upregulation of beta-catenin signaling in articular chondrocytes is most likely responsible for the conversion of normal articular chondrocytes into maturing (arthritic) chondrocytes, which is associated with activation of chondrocyte maturational genes and matrix degradation. Conditional activation of the beta-catenin gene in articular chondrocytes leads to an OA-like phenotype. Overexpression of Smurf2, an E3 ubiquitin ligase, also induces an OA-like phenotype through upregulation of beta-catenin signaling. In addition, beta-catenin upregulation was also found in articular cartilage tissues in patients with OA. These findings indicate that beta-catenin plays a central role in articular cartilage function and that activation of beta-catenin signaling may represent a pathologic mechanism for OA development.
Wu
Qiuqian
Q
Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Zhu
Mei
M
Rosier
Randy N
RN
Zuscik
Michael J
MJ
O'Keefe
Regis J
RJ
Chen
Di
D
D000818:Animals; D002356:Cartilage / Q000378:metabolism / Q000502:physiology*; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D051176:beta Catenin; C533325:Smurf2 protein, mouse; D044767:Ubiquitin-Protein Ligases
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