G-Protein Coupled Receptor 35 Induces Intervertebral Disc Degeneration by Mediating the Influx of Calcium Ions and Upregulating Reactive Oxygen Species.

Abstract	Intervertebral disc degeneration (IDD) is a chronic disease affecting millions of patients; however, its specific etiology is unknown. G protein-coupled receptors (GPRs) are a superfamily of integral membrane receptors in cells, and the receptors respond to a diverse range of stimuli and participate in multiple cellular activities. Here, using RNA-sequencing (RNA-seq) methods and immunohistochemistry, we revealed that G protein-coupled receptor 35 (GPR35) may have a relationship with IDD. Then, we demonstrated that the deletion of GPR35 in nucleus pulposus cells (NPCs) with siRNA or in Gpr35-/- mice significantly alleviated IDD caused by senescence or mechanical stress, further validating the pathological role of GPR35 in IDD. In addition, GPR35 induced the influx of Ca2+ and upregulation of reactive oxygen species (ROS) under mechanical stress in NPCs, which we believe to be the mechanism of GPR35-induced IDD. Finally, GPR35 caused upregulation of ROS in NPCs under mechanical stress, while excessive ROS stimulated the NPCs to express more GPR35 with a significant dose or time response. The u-regulated GPR35 could sense mechanical stress to produce more ROS and perpetuate this harmful cycle. In summary, our study shows that GPR35 plays a critical role in mediating IDD via mediating the influx of calcium ions and upregulating ROS, which implies a strong potential advantage of GPR35 as a prevention and treatment target in IDD.
Authors	Zhe Chen, Yucheng Jiao, Ying Zhang, Qingfeng Wang, Wenjian Wu, Jiancheng Zheng, Jitian Li
Journal	Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 5469220 ( 2022) ISSN: 1942-0994 [Electronic] United States
PMID	35087615 (Publication Type: Journal Article)
Copyright	Copyright © 2022 Zhe Chen et al.
Chemical References	Reactive Oxygen Species Receptors, G-Protein-Coupled Calcium
Topics	Animals Calcium (metabolism) Humans Intervertebral Disc Degeneration (physiopathology) Male Mice Reactive Oxygen Species (metabolism) Receptors, G-Protein-Coupled (metabolism)

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