Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis

Nat Clin Pract Rheumatol. 2008 Oct;4(10):550-6. doi: 10.1038/ncprheum0904.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mice
  • Osteoarthritis / etiology*
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism
  • Polymorphism, Genetic
  • Signal Transduction
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • CTNNB1 protein, human
  • Wnt Proteins
  • beta Catenin