Elsevier

Laboratory Investigation

Volume 96, Issue 2, February 2016, Pages 186-196
Laboratory Investigation

Pathobiology in Focus
Wnt signaling in cartilage development and diseases: lessons from animal studies

https://doi.org/10.1038/labinvest.2015.142Get rights and content
Under an Elsevier user license
open archive

Abstract

Cartilage not only plays essential roles in skeletal development and growth during pre- and postnatal stages but also serves to provide smooth movement of skeletons throughout life. Thus, dysfunction of cartilage causes a variety of skeletal disorders. Results from animal studies reveal that β-catenin-dependent canonical and independent non-canonical Wnt signaling pathways have multiple roles in regulation of cartilage development, growth, and maintenance. β-Catenin-dependent signaling is required for progression of endochondral ossification and growth of axial and appendicular skeletons, while excessive activation of this signaling can cause severe inhibition of initial cartilage formation and growth plate organization and function in mice. In contrast, non-canonical Wnt signaling is important in columnar organization of growth plate chondrocytes. Manipulation of Wnt signaling causes or ameliorates articular cartilage degeneration in rodent osteoarthritis models. Human genetic studies indicate that Wnt/β-catenin signaling is a risk factor for osteoarthritis. Accumulative findings from analysis of expression of Wnt signaling molecules and in vivo and in vitro functional experiments suggest that Wnt signaling is a therapeutic target for osteoarthritis. The target tissues of Wnt signaling may be not only articular cartilage but also synovium and subchondral bone.

Cited by (0)

This review focuses on Wnt signaling in cartilage development and skeletal disorders involving cartilage. It describes the essential roles of cartilage in formation, growth and function of long bones; Wnt signaling in growth plate cartilage during long bone development and growth; and Wnt signaling in osteoarthritis.