Fig. 1.

Proposed targets of glucagon-like peptide-1 (GLP-1) in joint tissues. Anatomical illustration of osteoarthritis knee joint structure including the main contributing tissues and their interactions. The cell-specific roles and molecular effects of GLP-1 in the GLP-1 receptor (GLP-1R)-dependent pathway may help counteract the pathogenesis of osteoarthritis (OA) in cartilage, synovial membrane, Hoffa's fat pad and bone tissue. GLP-1R is expressed in chondrocytes, macrophages, adipocytes and the osteocyte surface. G protein-coupled receptor 120 (GPR-120) is also expressed on the chondrocyte surface. GLP-1 or GLP-1 analogues mediate their effects by binding to the GLP-1R. The main effects lead to inhibition of cytokine secretion into the synovial fluid, thus decreasing inflammation and consequently reducing other downstream effects such as oxidative stress, pro-degradative mediator secretion, phenotype modification (hypertrophy, M1/M2 macrophage phenotype, fibrosis) or impairment/destruction of joint cells (apoptosis, senescence). GLP-1 or GLP-1 analogues can also induce anabolic mechanisms such as cell proliferation and differentiation, mineralization or healing.