Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 677, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2019.108164
Keywords
GPR39; G coupled-protein receptor; Osteoarthritis; Extracellular matrix; Type II collagen; Aggrecan; MAPK p38/NF-kappa B
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Funding
- National Natural Science Foundation of China [81603599, 81774038]
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Excessive degradation of the cartilage articular extracellular matrix (ECM) in chondrocytes has been considered as an important pathological characteristics of OA. In the present study, we demonstrate that the G protein-coupled receptor GPR39 is expressed on SW1353 chondrocytes and is significantly downregulated in response to advanced glycation end products (AGEs). Our findings show that agonism of GPR39 exerts significant protective effects against AGE-induced degradation of articular extracellular matrix. Agonism of GPR39 rescued degradation of type II collagen by decreasing expression of the collagen-degrading enzymes matrix metalloproteinase (MMP)-3 and MMP-13. Additionally, agonism of GPR39 rescued AGE-induced suppression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Agonism of GPR39 prevented degradation of aggrecan by downregulating AGE-induced expression of a disintegrin and metalloproteinase with type I thrombospondin motif (ADAMTS)-4 and ADAMTS-5. Finally, we demonstrate that the effects of GPR39 are mediated through the p38 mitogen activated protein kinase (MAPK)/nuclear factor-kappa B (NF-kappa B) cellular signaling pathway. Taken together, our findings show for the first time that targeted therapies involving GPR39 may provide a novel approach for the prevention and treatment of osteoarthritis.
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