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Papers of the Week

Papers: 29 Jul 2023 - 4 Aug 2023

2023 Jul

Acta Pharm Sin B




GPRC5B protects osteoarthritis by regulation of autophagy signaling.


He L, Xu Z, Niu X, Li R, Wang F, You Y, Gao J, Zhao L, Shah KM, Fan J, Liu M, Luo J


Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes . Furthermore, mice deficient in displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our findings. Overexpression of by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.