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G protein\u2010coupled 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\u2010sequencing (RNA\u2010seq) methods and immunohistochemistry, we revealed that G protein\u2010coupled receptor 35 (GPR35) may have a relationship with IDD. Then, we demonstrated that the deletion of <jats:italic>GPR35<\/jats:italic> in nucleus pulposus cells (NPCs) with siRNA or in <jats:italic>Gpr35<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice significantly alleviated IDD caused by senescence or mechanical stress, further validating the pathological role of <jats:italic>GPR35<\/jats:italic> in IDD. In addition, <jats:italic>GPR35<\/jats:italic> induced the influx of Ca<jats:sup>2+<\/jats:sup> and upregulation of reactive oxygen species (ROS) under mechanical stress in NPCs, which we believe to be the mechanism of GPR35\u2010induced 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\u2010regulated 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.<\/jats:p>","DOI":"10.1155\/2022\/5469220","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T23:20:13Z","timestamp":1642548013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["G\u2010Protein Coupled Receptor 35 Induces Intervertebral Disc Degeneration by Mediating the Influx of Calcium Ions and Upregulating Reactive Oxygen Species"],"prefix":"10.1155","volume":"2022","author":[{"given":"Zhe","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yucheng","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingfeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5325-1186","authenticated-orcid":false,"given":"Wenjian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8932-1876","authenticated-orcid":false,"given":"Jiancheng","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9857-3226","authenticated-orcid":false,"given":"Jitian","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,1,18]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2451051706"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-015-9986-4"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2017.01.001"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-016-3115-5"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2019.08.005"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.4161\/psb.4.10.9530"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-021-00360-w"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6681815"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.03.084"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.120.15423"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66417-8"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm756"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2014.1000134"},{"key":"e_1_2_11_14_2","doi-asserted-by":"crossref","unstructured":"WangS. 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