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IVDD progression involves pathological shifts marked by low-grade inflammation, extracellular matrix remodeling, and metabolic disruptions characterized by heightened glycolytic pathways, mitochondrial dysfunction, and cellular senescence. Extensive posttranslational modifications of proteins within nucleus pulposus cells and chondrocytes play crucial roles in reshaping the intervertebral disc phenotype and orchestrating metabolism and inflammation in diverse contexts. This review focuses on the pivotal roles of phosphorylation, ubiquitination, acetylation, glycosylation, methylation, and lactylation in IVDD pathogenesis. It integrates the latest insights into various posttranslational modification-mediated metabolic and inflammatory signaling networks, laying the groundwork for targeted proteomics and metabolomics for IVDD treatment. The discussion also highlights unexplored territories, emphasizing the need for future research, particularly in understanding the role of lactylation in intervertebral disc health, an area currently shrouded in mystery.<\/jats:p>","DOI":"10.34133\/research.0350","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T15:32:06Z","timestamp":1710948726000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":46,"title":["Altered Metabolism and Inflammation Driven by Post-translational Modifications in Intervertebral Disc Degeneration"],"prefix":"10.34133","volume":"7","author":[{"given":"Dingchao","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaizhen","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Wuhan University, Wuhan 430072, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaocai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-614X","authenticated-orcid":false,"given":"Cao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2024,4,5]]},"reference":[{"issue":"10294","key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/S0140-6736(21)00733-9","article-title":"Low back pain","volume":"398","author":"Knezevic NN","year":"2021","unstructured":"Knezevic NN, Candido KD, Vlaeyen JWS, Zundert JV, Cohen SP. 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