Featured Article: Deficiency of G-protein coupled receptor 40, a lipid-activated receptor, heightens in vitro- and in vivo-induced murine osteoarthritis

摘要: Osteoarthritis (OA) is an age-related degenerative joint disease. To date, its management focused on symptoms (pain and inflammation). Studies suggest that fatty acids can reduce the expression of inflammatory catalytic mediators, improve in vivo function. Free acid receptors (FFARs) such as G-protein coupled receptor 40 (GPR40) are proposed attractive therapeutic targets to counteract inflammation cartilage degradation observed in OA. This study aims elucidate involvement GPR40 In this study, we used in vitro model OA, surgically induced OA by ligament transection partial meniscectomy wild-type deficient mice. phenotype was investigated histology genes expression. We demonstrate IL-1β-treated GPR40(-/-) chondrocytes secret more mediators (nitric oxide, interleukin-6, prostaglandin E2) active catabolic enzymes (metalloproteinase-2, -9 [MMP-2, MMP-9]), show decreased anabolism (glycoaminoglycan) compared GPR40(+/+) cells. accordance with these results, mice exhibit aggravated OA-induced characterized higher tidemark exposure, frequency osteophyte formation subchondral bone sclerosis. Altogether our results deficiency leads extended phenotype, providing evidence increasing activity, natural or synthetic ligands, could be a new strategy