WNT signaling and chondrocytes: from cell fate determination to osteoarthritis physiopathology

Abstract

Context: Osteoarthritis (OA) is an articular disorder leading to the degradation of articular cartilage phenotypical chondrocytes modifications, including the acquisition of a fibroblast-like morphology, decreased expression of collagen type II, and increased expression of fetal collagen type I, metalloproteinase 13 and nitric oxide synthase. This promotes matrix degradation and unsuccessful cartilage repair. WNT signaling constitutes one of the most critical biological processes during cell fate assignment and homeostasis.

Objectives: This review aims to give an insight on results from the studies that were interested in the involvement of WNT in OA.

Methods: Studies were selected through a pubmed search.

Results: Recent genetic data showed that aberration in WNT signaling may be involved in OA. WNT signals are transduced through at least three cascades: the canonical WNT/β-catenin pathway, the WNT/Ca(2+) pathway and the WNT/planar cell polarity pathway. Most of the studies used in-vitro models to elucidate the involvement of WNT in the physiopathology of OA. These studies analyzed the expression pattern of WNT pathway components during OA such as WNT5, WNT7, co-receptor LRP, β-catenin, WNT target genes (c-jun, cyclins) and/or the interaction of these components with the secretion of OA most important markers such as IL-1, collagens, MMPs. Results from these studies are in favor of a deep involvement of the WNT signaling in the physiopathology of OA either by having a protective or a destructive role.

Conclusion: Deeper researches may eventually allow scientists to target WNT pathway in order to help develop efficient therapeutic approaches to treat OA.