|  | Effect on |  |  |
---|---|---|---|---|
 | Element treatment/SNPs | Wnt signaling | Results | Conclusions |
Receptor | Â | Â | Â | Â |
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 | Â | Â | Â | Â |
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 | Â | Â | Â | Â |
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 | Â | Â | Â | Â |
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] |