GPRC5B protects osteoarthritis by regulation of autophagy signaling.
10.1016/j.apsb.2023.05.014
- Author:
Liang HE
1
;
Ziwei XU
2
;
Xin NIU
2
;
Rong LI
1
;
Fanhua WANG
1
;
Yu YOU
2
;
Jingduo GAO
2
;
Lei ZHAO
1
;
Karan M SHAH
3
;
Jian FAN
4
;
Mingyao LIU
2
;
Jian LUO
1
Author Information
1. Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai 201613, China.
2. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
3. Department of Oncology and Metabolism, the Medical School, the University of Sheffield, Sheffield S10 2TN, UK.
4. Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Shanghai 200092, China.
- Publication Type:Journal Article
- Keywords:
Autophagy;
Cartilage;
Cartilage anabolism and catabolism;
Cartilage regeneration;
Chondrocyte;
Drug target;
GPRC5B;
Osteoarthritis
- From:
Acta Pharmaceutica Sinica B
2023;13(7):2976-2989
- CountryChina
- Language:English
-
Abstract:
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 Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b 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 in vitro findings. Overexpression of Gprc5b 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 Gprc5b 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.
