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Table 1 Overview of the roles of various elements of the Wnt signaling pathway in osteoarthritis development, as demonstrated by human genetic studies or animal models

From: Wnt and Rho GTPase signaling in osteoarthritis development and intervention: implications for diagnosis and therapy

   Effect on   
  Element treatment/SNPs Wnt signaling Results Conclusions
Receptor     
LRP5 Haplotype (C-G-C-C-A) in LRP5 Inhibition This haplotype predisposes to increased risk of OA LRP5 variant may predispose patients to OA [56]
  Lrp5 knockout in mice Inhibition Increased cartilage degradation, decreased bone mineral density Loss of function of Lrp5 leads to OA [57]
Wnt ligands     
Wnts (up-regulated in OA) Mechanical injury Activation Up-regulation of Wnt16/WISP-1, down-regulation of FRZB, up- regulation of β-catenin, axin-2, C-JUN and LEF-1 Mechanical injury activates Wnt signaling [43]
Wnt antagonists     
Frzb (up-regulated in OA) Arg200Trp/Arg324Gly Frzb variants Activation These two variants are associated with female hip OA from an epidemiological viewpoint These two variants confer genetic susceptibility to female hip OA [46, 47]
  Arg200Trp/Arg324Gly Frzb variants Activation These two variants are associated with other generalized OA by epidemiological analysis These two variants contribute to female hip OA [50]
  Frzb knockout mice Activation Increased cartilage damage, thicker cortical bone formation Loss of function of Frzb contributes to the development of OA [51]
DKK1 (up-regulated in OA) Inhibition of DKK1 by antibody Activation Blocks bone erosion, promotes bone formation, reverses RA to OA Wnt signaling is a key regulator of joint remodeling [53]
  OA rat knees were treated with end-capped phosphorothioate Dkk-1 antisense oligonucleotide (Dkk-1-AS) Inhibition Alleviated Mankin score, cartilage fibrillation, and serum cartilage degradation markers Dkk1 expression prevents OA cartilage destruction and subchondral bone damage [54]
Transcription factor     
β-Catenin (up- regulated in OA) Activation of β-catenin in articular chondrocytes Activation OA-like cartilage degradation, osteophyte formation, accelerated chondrocyte maturation and MMP13 expression Wnt/β-catenin activation promotes OA development by accelerating chondrocyte maturation [58]
  Suppression of β-catenin in articular chondrocytes Inhibition OA-like cartilage degradation, increased chondrocyte apoptosis Wnt/β-catenin inhibition promotes OA development by increasing chondrocyte apoptosis [59]
  1. LEF, lymphoid enhancing factor; MMP, matrix metalloproteinase; OA, osteoarthritis; RA, rheumatoid arthritis.