TABLE 1.
Novel roles of GPCRs in OA.
| GPCR family | GPCRs | Roles in pathogenesis of OA | Latent regulators | References |
| CKRs | CCR3 | High concentrations inactivated cAMP/PKA and activated ERK and p38 MAPK, while at low concentrations activated PI3K and JNK MAPK to up-regulate MMP-3 | U0126 SB203580 | Chao et al., 2011 |
| CXCR4 | Up-regulated the expression and release of MMP-3, MMP-9 and MMP-13, thus promoting the degradation and destruction of cartilage matrix | AMD3100 | Yang et al., 2020 | |
| CXCR7 | Promoted chondrocyte hypertrophy, cartilage angiogenesis, cartilage matrix degradation, inflammation and endochondral ossification | NA | Jones et al., 2006 | |
| EDGs | EDG1/3/5/6/8 | Increased PGE2 induced by COX-2 and MAPK to inhibit the expression of proteoglycan | NA | Masuko et al., 2007 |
| EDG2 | Increased the expression of inflammatory cytokines and MMPs in synovial cells | NA | Mototani et al., 2008 | |
| CBs | CB2 | Down-regulated MMP3 and MMP13 to improve subchondral bone morphology and underlying cartilage biochemical changes | HU308 WIN55,212-2 | Mlost et al., 2021 |
| PARs | PAR2 | Inhibited apoptosis by activating P38/MAPK, NF-κB and PI3K/AKT/mTOR mediated autophagy in chondrocytes | AZ3451 | Huang et al., 2019; Yan et al., 2020 |
| Bradykinin receptors | B2 receptor | Led to pain and inflammation in the synovium | Icatibant MEN16132 | Cucchi et al., 2005; Song et al., 2009 |
| MCRs | MC1R | MC1R-deficient led to loss of collagen II and the increase of MMP-13 and pro-inflammatory cytokines and accelerated cartilage matrix changes | BMS-470539 C-terminal KPV | Lorenz et al., 2014 |
| MC3R | Inhibited the release of proinflammatory cytokines and MMPs | [DTrp8]-γ-MSH PG-990 | Can et al., 2020 | |
| Secretin receptors | CTR | The expression of CTR in OA patients is significantly higher than that in normal controls | NA | Zupan et al., 2012 |
CKRs, chemokine receptors; CCR, C-C chemokine receptor; CXCR, C-X-C chemokine receptor; EDGs, endothelial differentiation G-protein coupled receptors; CBs, cannabinoid receptors; PARs, protease activated receptors; MCRs, melanocortin receptors; MMP, matrix metalloproteinases; SNP, single nucleotide polymorphism; ECM, extracellular matrix; NA, not available.