Fig. 1

Pathogenesis in OA related to CCLs and CCRs. CCLs and CCRs participate in the pathogenesis and development of OA through multiple mechanisms. CCL binds to specific CCR, activating downstream biochemical processes via the G-protein-coupled pathway (A), which promotes chondrocyte apoptosis (B) and upregulates the expression of multiple matrix-degrading enzymes in the cartilage. The binding of CCL and CCR also induces the infiltration of various immune cells into the damaged joint, leading to local inflammation (C). At the nerve endings in the joint, the binding of CCL and CCR, as well as other related cell factors such as NGF and its receptor TrkA (D), leads to the release of neurotransmitters in the spinal cord, causing pain hypersensitivity. CCL, CC motif chemokine ligand; CCR, CC motif chemokine ligands receptor; OA, osteoarthritis; NGF, nerve growth factor; TrkA, tropomyosin receptor kinase A; DRG, dorsal root ganglia