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This condition is a significant contributor to low back pain, which poses a substantial burden on both personal quality of life and societal economics. Changes in the number and function of ion channels can disrupt the water and ion balance both inside and outside cells, thereby impacting the physiological functions of tissues and organs. Therefore, maintaining ion homeostasis and stable expression of ion channels within the cellular microenvironment may prove beneficial in the treatment of disc degeneration. Aquaporin (AQP), calcium ion channels, and acid-sensitive ion channels (ASIC) play crucial roles in regulating water, calcium ions, and hydrogen ions levels. These channels have significant effects on physiological and pathological processes such as cellular aging, inflammatory response, stromal decomposition, endoplasmic reticulum stress, and accumulation of cell metabolites. Additionally, Piezo 1, transient receptor potential vanilloid type 4 (TRPV4), tension response enhancer binding protein (TonEBP), potassium ions, zinc ions, and tungsten all play a role in the process of intervertebral disc degeneration. This review endeavors to elucidate alterations in the microenvironment of the nucleus pulposus during intervertebral disc degeneration (IVDD), with a view to offer novel insights and approaches for exploring therapeutic interventions against disc degeneration.<\/jats:p>","DOI":"10.3390\/ijms242316592","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T03:54:37Z","timestamp":1700625277000},"page":"16592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Achilles\u2019 Heel\u2014The Significance of Maintaining Microenvironmental Homeostasis in the Nucleus Pulposus for Intervertebral Discs"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3740-3703","authenticated-orcid":false,"given":"Zhangbin","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, China"},{"name":"The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, China"},{"name":"The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3193-0297","authenticated-orcid":false,"given":"Guangzhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, China"},{"name":"The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-6328","authenticated-orcid":false,"given":"Haiwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8520-2282","authenticated-orcid":false,"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, China"},{"name":"The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewen","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, China"},{"name":"The Second Clinical Medical College, Lanzhou University, Lanzhou 730030, China"},{"name":"Key Laboratory of Orthopedics Disease of Gansu Province, Lanzhou University Second Hospital, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1016\/S0140-6736(20)32340-0","article-title":"Global estimates of the need for rehabilitation based on the Global Burden of Disease study 2019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"396","author":"Cieza","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103361","DOI":"10.1016\/j.autrev.2023.103361","article-title":"Global burden and risk factors of musculoskeletal disorders among adolescents and young adults in 204 countries and territories, 1990\u20132019","volume":"22","author":"Guan","year":"2023","journal-title":"Autoimmun. 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