Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis.
Osteoarthritis (OA) is a progressively degenerative joint condition that is influenced by various metabolic and structural factors. The canonical Wnt-frizzled-beta-catenin pathway has been implicated in the pathogenesis of OA. Products of the Wnt, frizzled, secreted frizzled-related protein (sFRP), Dickkopf and LDL-receptor-related protein gene families have crucial roles in the development and maintenance of bone, cartilage and joints. Increased levels of beta-catenin have been observed in degenerative cartilage, suggesting that a diminished capacity to limit Wnt signaling might contribute to cartilage loss. Polymorphisms in genes involved in Wnt signaling-particularly in the gene encoding sFRP-3-are associated with an increased susceptibility to the development of OA. At least one of these polymorphisms in the gene encoding sFPR-3 is associated with a reduced ability to limit beta-catenin signaling. In addition, the canonical Wnt signaling pathway is influenced by local factors, including alterations in glycosaminoglycan sulfation, cartilage matrix content, transforming growth factor beta and vitamin D. A higher circulating level of the Wnt inhibitor Dickkopf-1, for instance, is associated with slowed progression of hip OA. Hence, the sum of local and systemic factors contributes to the outcome of the Wnt-frizzled pathways. Further investigation is needed to fully define the role of Wnt signaling in OA.
Corr
Maripat
M
Department of Medicine, Division of Rheumatology, Allergy and Rheumatology, University of California at San Diego, La Jolla, CA 92093-0663, USA. mcorr@ucsd.edu
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D010003:Osteoarthritis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495270:CTNNB1 protein, human; D051153:Wnt Proteins; D051176:beta Catenin