Wnt/β-catenin Signaling in Osteoarthritis and in Other Forms of Arthritis

Abstract

Purpose of Review Arthritis defines a large group of diseases primarily affecting the joint. It is the leading cause of pain and disability in adults. Osteoarthritis (OA) affecting the knee or hip is the most common form among over 100 types of arthritis. Other types of arthritis include erosive hand OA, tempo-romandibular joint (TMJ) OA, facet joint OA, diffuse idiopathic skeletal hyperostosis (DISH), and spondyloarthritis (SpA). However, the specific molecular signals involved in the development and progression of OA and related forms of arthritis remain largely unknown. The canonical wingless/integrated (Wnt)/β-catenin signaling pathway could play a unique role in the pathogenesis of arthritis. In this review article, we will focus on the molecular mechanisms of Wnt/β-catenin signaling in the pathogenesis of OA and other types of arthritis. Recent Findings Emerging evidence demonstrates that Wnts and Wnt-related molecules are involved in arthritis development and progression in human genetic studies and in vitro studies. Also, mouse models have been generated to determine the role of Wnt/β-catenin signaling in the pathogenesis of arthritis. Summary Wnt/β-catenin signaling represents a unique signaling pathway regulating arthritis development and progression, and the molecules in this particular pathway may serve as targets for the therapeutic intervention of arthritis. Mediators and downstream effectors of Wnt/β-catenin signaling are increased in OA as well other forms of arthritis, including DISH and SpA. Through extensive investigations, including pre-clinical studies in transgenic mice and translational and human studies, the Wnt/β-catenin signaling pathway has been proven to play roles in bone and joint pathology by directly affecting bone, cartilage, and synovial tissue; further, these pathologies can be reduced through targeting this pathway. Continued investigation into the distinct molecular signaling of the Wnt/β-catenin pathway will provide additional insights toward the therapeutic intervention in arthritis.

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

“…Notably, Wnt/β-catenin signaling, which contributes to the extracellular matrix damage process and chondrocyte destruction in the etiology and pathogenesis of OA [22, 23], was effectively inhibited by ART. Some FDA-approved drugs, such as verapamil, are Wnt antagonists which hold promise in OA therapy [44].…”

“…Evidence also suggests that ART exerts anti-inflammatory and anti-tumor effects by suppressing the Wnt/β-catenin signaling pathway, which is well established as a crucial pathway regulating the pathogenesis of OA [21, 22]. The canonical Wnt pathway triggers its signaling within chondrocytes by regulating intracellular level and subcellular localization of β-catenin [23, 24].…”

Variations of Wnt/β‐catenin pathway‐related genes in susceptibility to knee osteoarthritis: A three‐centre case‐control study

“…β‐catenin‐dependent canonical and independent non‐canonical Wnt signalling pathways play multiple roles in regulating the cartilage development, growth and maintenance in animal models . Alterations in genes associated with Wnt/β‐catenin signalling were suggested as susceptibility factors for OA development . Some SNPs of Wnt‐related genes influence the genetic predisposition to OA.…”

“…suggested as susceptibility factors for OA development. 16 Some SNPs of Wnt-related genes influence the genetic predisposition to OA. Therefore, 13 studies changed their focus to the association of polymorphisms in pathway-related genes with risk of OA.…”

Concise Review: TLR Pathway-miRNA Interplay in Mesenchymal Stromal Cells: Regulatory Roles and Therapeutic Directions

“…For instance, miR‐335‐5p, whose expression is modulated by TLR2 or TLR4 stimulation in BM‐MSCs (upregulated by TLR2 and downregulated by TLR4 activations) , activates Wnt pathway by repressing DKK1 (Wnt pathway antagonist). Wnt/β‐catenin signaling is central to osteogenic differentiation and plays a role in the pathogenesis of many human diseases, including osteoarthritis (OA) . Regulation of DKK proteins in Wnt‐mediated cell differentiation, however, is specific to cell type and developmental stage .…”