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 example… Show more
“…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 ].…”
“…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 ].…”
“…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).…”
Section: Biochemical Cascades and Signalling Pathways Of Monocyte/mac...mentioning
Osteoarthritis (OA) is one of the most common degenerative diseases characterised by joint pain, swelling and decreased mobility, with its main pathological features being articular synovitis, cartilage degeneration and osteophyte formation. Inflammatory cytokines and chemokines secreted by activated immunocytes can trigger various inflammatory and immune responses in articular cartilage and synovium, contributing to the genesis and development of OA. A series of monocyte/macrophage chemokines, including monocyte chemotaxis protein (MCP)‐1/CCL2, MCP2/CCL8, macrophage inflammatory protein (MIP)‐1α/CCL3, MIP‐1β/CCL4, MIP‐3α/CCL20, regulated upon activation, normal T‐cell expressed and secreted /CCL5, CCL17 and macrophage‐derived chemokine/CCL22, was proven to transmit cell signals by binding to G protein–coupled receptors on recipient cell surface, mediating and promoting inflammation in OA joints. However, the underlying mechanism of these chemokines in the pathogenesis of OA remains still elusive. Here, published literature was reviewed, and the function and mechanisms of monocyte/macrophage chemokines in OA pathogenesis were summarised. The symptoms and disease progression of OA were found to be effectively alleviated when the expression of these chemokines is inhibited. Elucidating these mechanisms could contribute to further understand how OA develops and provide potential targets for the early diagnosis of arthritis and drug treatment to delay or even halt OA progression.
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