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.
