G Protein-Coupled Receptors in Osteoarthritis

Abstract

Osteoarthritis (OA) is the most common chronic joint disease characterized, for which there are no available therapies being able to modify the progression of OA and prevent long-term disability. Critical roles of G-protein coupled receptors (GPCRs) have been established in OA cartilage degeneration, subchondral bone sclerosis and chronic pain. In this review, we describe the pathophysiological processes targeted by GPCRs in OA, along with related preclinical model and/or clinical trial data. We review examples of GPCRs which may offer attractive therapeutic strategies for OA, including receptors for cannabinoids, hormones, prostaglandins, fatty acids, adenosines, chemokines, and discuss the main challenges for developing these therapies.

Identification and validation of immune-related genes in osteoarthritic synovial fibroblasts

“…Closely connected cytokine clusters in the OA-PPI network were identified using MCODE cluster analysis. We identified nine terms that were highly correlated with inflammatory signaling pathways, cell adhesion, and signal transduction, including the terms “G proton-coupled peptide receptor activity,” “PI3K-Akt signaling pathway,” and “ionotropic glutamate receiver complex.” G-protein-coupled receptors—transmembrane receptors that play pivotal roles in inflammation and immune responses [ 30 ], including in RA and OA—are involved in various OA pathologies, such as cartilage matrix degradation, synovitis, subchondral bone remodeling, and osteophyte formation [ 31 , 32 ]. Inhibition of G protein binding suppresses collagen-induced arthritis by reducing CD4+T cell productions [ 33 ].…”

The role of monocyte/macrophage chemokines in pathogenesis of osteoarthritis: A review

“…When monocyte/macrophage chemokines bind to G protein–coupled receptors on the surface of cell membranes, they induce the conversion between guanosine diphosphate and triphosphate on the Gα subunit, which subsequently activate the downstream pathway, including adenylate cyclase‐cyclic adenosine monophosphate‐protein kinase A pathway and phospholipase C‐IP3‐PKC signalling pathways (Gilchrist, 2020; Zhang et al., 2023), forming complex regulatory networks and leading to phenotypic changes through biochemical cascades, as shown in Table 2 (Wang et al., 2021).…”