{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:02:55Z","timestamp":1785416575357,"version":"3.56.0"},"reference-count":13,"publisher":"IMR Press","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82472494"],"award-info":[{"award-number":["82472494"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background:Intervertebral disc degeneration (IDD) is a major pathological contributor to low back pain, and its progression is closely associated with oxidative stress and cell death. Ferroptosis is a form of programmed cell death characterized by iron-dependent lipid peroxidation, which has recently been confirmed to participate in IDD progression. Microsomal glutathione S-transferase 1 (MGST1) plays an important role in glutathione metabolism and cellular antioxidant defense, but its function in IDD remains unclear. This study aimed to investigate the expression profile of MGST1 in IDD and to elucidate its molecular mechanism in delaying degeneration by regulating ferroptosis.Methods:Differentially expressed ferroptosis-related genes associated with intervertebral disc degeneration were screened through bioinformatics analysis. MGST1 expression changes were validated using a needle puncture-induced rat IDD model and a degenerated nucleus pulposus (NP) cell model. MGST1 knockdown and overexpression strategies were employed to evaluate its effects on the extracellular matrix metabolism, apoptosis, and senescence of nucleus pulposus cells. Further examinations of ferroptosis-related indicators were conducted, including levels of lipid peroxidation, reactive oxygen species generation, intracellular Fe2+ content, and changes in mitochondrial membrane potential. For in vivo experiments, the therapeutic effect of MGST1 overexpression was assessed by intradiscal injection of an MGST1-overexpressing lentivirus into the rat intervertebral disc degeneration model.Results:Bioinformatics analysis indicated that MGST1 is a key candidate gene in IDD. MGST1 expression was consistently upregulated with increasing degeneration severity in rat disc tissues and degenerated NP cells. Knockdown of MGST1 significantly promoted extracellular matrix degradation and increased apoptosis and senescence levels in NP cells, while MGST1 overexpression markedly improved these changes. Mechanistic studies revealed that MGST1 deficiency significantly enhanced ferroptosis characteristics in NP cells, including accumulation of lipid peroxides and ROS, increased Fe2+ content, and decreased mitochondrial membrane potential. In vivo experiments demonstrated that MGST1 overexpression significantly alleviated the degree of IDD in rats.Conclusion:MGST1 exhibits compensatory upregulation during the progression of intervertebral disc degeneration and delays its progression by inhibiting ferroptosis in nucleus pulposus cells. This study reveals a novel mechanism by which MGST1 regulates ferroptosis in IDD and provides a potential molecular target for the prevention and treatment of IDD.<\/jats:p>","DOI":"10.31083\/fbl50880","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:17:49Z","timestamp":1785413869000},"source":"Crossref","is-referenced-by-count":0,"title":["MGST1 Suppresses Ferroptosis in Nucleus Pulposus Cells and Attenuates Intervertebral Disc Degeneration by Regulating GPX4"],"prefix":"10.31083","volume":"31","author":[{"given":"Zhenxin","family":"Huo","sequence":"first","affiliation":[{"name":"Department of Graduate School, Clinical College of Orthopedics, Tianjin Medical University, 300070 Tianjin, China"},{"name":"Department of Minimally Invasive Spine Surgery, Tianjin Hospital, Tianjin University, 300211 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Graduate School, Clinical College of Orthopedics, Tianjin Medical University, 300070 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Graduate School, Clinical College of Orthopedics, Tianjin Medical University, 300070 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4407-8745","authenticated-orcid":true,"given":"Baoshan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Graduate School, Clinical College of Orthopedics, Tianjin Medical University, 300070 Tianjin, China"},{"name":"Department of Minimally Invasive Spine Surgery, Tianjin Hospital, Tianjin University, 300211 Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"The Lancet Rheumatology. 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European Journal of Pharmacology. 2024; 964: 176298.","DOI":"10.1016\/j.ejphar.2023.176298"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annual Review of Pharmacology and Toxicology. 2005; 45: 51\u201388.","DOI":"10.1146\/annurev.pharmtox.45.120403.095857"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Huo Z, Li D, Zhang K, Yan B, Zhang T, Li Z, et al. MGST1 May Regulate the Ferroptosis of the Annulus Fibrosus of Intervertebral Disc: Bioinformatic Integrated Analysis and Validation. Frontiers in Bioscience (Landmark Edition). 2024; 29: 224.","DOI":"10.31083\/j.fbl2906224"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Zhou N, Yuan X, Du Q, Zhang Z, Shi X, Bao J, et al. FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations. Nucleic Acids Research. 2023; 51: D571\u2013D582.","DOI":"10.1093\/nar\/gkac935"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Yang RZ, Xu WN, Zheng HL, Zheng XF, Li B, Jiang LS, et al. Involvement of oxidative stress-induced annulus fibrosus cell and nucleus pulposus cell ferroptosis in intervertebral disc degeneration pathogenesis. Journal of Cellular Physiology. 2021; 236: 2725\u20132739.","DOI":"10.1002\/jcp.30039"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Fan C, Chu G, Yu Z, Ji Z, Kong F, Yao L, et al. The role of ferroptosis in intervertebral disc degeneration. Frontiers in Cell and Developmental Biology. 2023; 11: 1219840.","DOI":"10.3389\/fcell.2023.1219840"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Yang WS, SriRamaratnam R, Welsch ME, Shimada AF, Skouta CB, Viswanathan LM, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014; 156: 317\u2013331.","DOI":"10.1016\/j.cell.2013.12.010"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/31\/7\/10.31083\/FBL50880","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:18:19Z","timestamp":1785413899000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/31\/7\/10.31083\/FBL50880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":13,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026]]}},"alternative-id":["S2768-6701(26)02136-2"],"URL":"https:\/\/doi.org\/10.31083\/fbl50880","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]},"article-number":"50880"}}