Wnt–β-catenin signaling in the pathogenesis of osteoarthritis

M Corr - Nature clinical practice Rheumatology, 2008 - nature.com
M Corr
Nature clinical practice Rheumatology, 2008nature.com
Osteoarthritis (OA) is a progressively degenerative joint condition that is influenced by
various metabolic and structural factors. The canonical Wnt–frizzled–β-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
β-catenin have been observed in degenerative cartilage, suggesting that a diminished …
Abstract
Osteoarthritis (OA) is a progressively degenerative joint condition that is influenced by various metabolic and structural factors. The canonical Wnt–frizzled–β-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 β-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 β-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 β 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.
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