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The role of Wnt proteins in arthritis

Nature Clinical Practice Rheumatology volume 4, pages 473–480 (2008)Cite this article

Abstract

Wnt proteins regulate organ development, tumorigenesis and bone homeostasis, among other functions. The binding of Wnt proteins to plasma membrane receptors on mesenchymal cells induces the differentiation of these cells into the osteoblast lineage and thereby supports bone formation. Wnts are also key signaling proteins in joint remodeling processes. Active Wnt signaling contributes to osteophyte formation and might have an essential role in the anabolic pattern of joint remodeling that is observed in ankylosing spondylitis and osteoarthritis. By contrast, blockade of Wnt signaling facilitates bone erosion and contributes to catabolic joint remodeling, a process that is observed in rheumatoid arthritis. This Review summarizes current knowledge of the molecular regulation of joint remodeling associated with chronic arthritis, focusing on the role of the Wnt proteins and their inhibitors. It also addresses the role of Wnt in determining the differences in clinical presentation of inflammatory arthropathies and discusses implications for future therapy.

Key Points

  • The balance of Wnt proteins and their antagonists is vital in osteoblast differentiation and bone formation

  • Arthritis leads to joint remodeling with either a decrease in local bone mass as observed in rheumatoid arthritis or an increase in local bone mass as observed in ankylosing spondylitis

  • Wnt proteins are crucial in driving osteophytic responses in arthritis, and their antagonists, such as DKK proteins, actively suppress osteophyte formation

  • Activity of Wnt signaling pathways is a key determinant of the pattern of structural remodeling in arthritis

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Figure 1: The canonical Wnt signaling pathway.
Figure 2: Wnt and joint remodeling.

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Author information

Authors and Affiliations

  1. G Schett is a Specialist in Rheumatology and Immunology and Chairman of the Department of Internal Medicine 3, J Zwerina is a Rheumatologist and J-P David is a Bone Biologist in the Department of Internal Medicine 3 at the University of Erlangen-Nuremberg, Erlangen, Germany.,

    Georg Schett, Jochen Zwerina & Jean-Pierre David

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  1. Georg Schett
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  2. Jochen Zwerina
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  3. Jean-Pierre David
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Correspondence to Georg Schett.

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Schett, G., Zwerina, J. & David, JP. The role of Wnt proteins in arthritis. Nat Rev Rheumatol 4, 473–480 (2008). https://doi.org/10.1038/ncprheum0881

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