Wnt signaling pathway in rheumatoid arthritis, with special emphasis on the different roles in synovial inflammation and bone remodeling

Abstract

Rheumatoid arthritis (RA) is a chronic symmetrical autoimmune disease of unknown etiology that affects primarily the diarthrodial joints. Characteristic features of RA pathogenesis are synovial inflammation and proliferation accompanied by cartilage erosion and bone loss. Fibroblast-like synoviocytes (FLS) display an important role in the pathogenesis of RA. Several lines of evidence show that the Wnt signaling pathway significantly participates in the RA pathogenesis. The Wnt proteins are glycoproteins that bind to the Fz receptors on the cell surface, which leads to several important biological functions, such as cell differentiation, embryonic development, limb development and joint formation. Accumulated evidence has suggested that this signaling pathway plays a key role in the FLS activation, bone resorption and joint destruction during RA development. Greater knowledge of the role of the Wnt signaling pathway in RA could improve understanding of the RA pathogenesis and the differences in RA clinical presentation and prognosis. In this review, new advances of the Wnt signaling pathway in RA pathogenesis are discussed, with special emphasis on its different roles in synovial inflammation and bone remodeling. Further studies are needed to reveal the important role of the members of the Wnt signaling pathway in the RA pathogenesis and treatment.

Keywords: 11beta-hydroxysteroid dehydrogenase type 1; 11β-HSD1; ACPA; APC; BMSC; CK1; CamKII; Cthrc1; DKK1; Dickkopf-1; Dvl; EZH2; FGF; FLS; Fibroblast-like synoviocytes; GSK3β; ILGF-1; LEF; LPS; LRP; MAPK; MITF; MMPs; MSCs; Osteoblasts; PADI4; PAR-2; PDB; PDGF; PKC; Paget's disease of the bone; RA; RANKL; ROK; Rheumatoid arthritis; Ror2; SDF-1; SFRP; Secreted frizzled-related protein; T-cell factors; T-cell receptor; TCFs; TCR; VCAM-1; VEGF; Wnt signaling pathway; Zeste homologue 2; adenomatous polyposis coli; alpha-Kelch-like ECT2-interacting protein; alphaKLEIP; anti-citrullinated peptide antibody; bone marrow stromal cell; calmodulin kinase II; casein kinase 1; collagen triple-helix repeat-containing 1; dickkopf-1; disheveled; fibroblast growth factor; fibroblast-like synoviocytes; glycogen synthase kinase 3β; hTERT; human telomerase reverse transcriptase; insulin like growth factor-1; lipopolysaccharide; low-density lipoprotein receptor protein; lymphoid enhancer binding factors; matrix metalloproteinases; mesenchymal stem cells; miRNA; microRNA; microphthalmia-associated transcription factor; mitogen-activated protein; peptidylarginine deiminase-4; platelet derived growth factor; protein kinase C; proteinase-activated receptor-2; receptor activator of NFκB ligand; receptor tyrosine kinase-like orphan receptor 2; rheumatoid arthritis; rho kinase; secreted frizzled-related protein; stromal cell derived factor 1; vascular cell adhesion molecule-1; vascular-endothelial growth factor.