{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:23:09Z","timestamp":1782282189253,"version":"3.54.5"},"reference-count":35,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jaseng Medical Foundation, Korea","award":["HF21C0100"],"award-info":[{"award-number":["HF21C0100"]}]},{"name":"Traditional Korean Medicine Research and Development Program of the Korean Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea","award":["HF21C0100"],"award-info":[{"award-number":["HF21C0100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Intervertebral disc degeneration (IDD) is an age-dependent progressive spinal disease that causes chronic back or neck pain. Although aging has long been presented as the main risk factor, the exact cause is not fully known. DNA methylation is associated with chronic pain, suggesting that epigenetic modulation may ameliorate disc degeneration. We examined histological changes in the DNA methylation within the discs and their association with pain-related transient receptor potential vanilloid subtype 1 (TrpV1) expression in rats subjected to IDD. Epigenetic markers (5-hydroxymethylcytosine (5hmC), 5-methylcytosine (5Mc)), DNA methyltransferases (DNMTs), and Ten-eleven translocations (Tets) were analyzed using immunohistochemistry, real-time PCR, and DNA dot-blot following IDD. Results revealed high 5mC levels in the annulus fibrosus (AF) region within the disc after IDD and an association with TrpV1 expression. DNMT1 is mainly involved in 5mC conversion in degenerated discs. However, 5hmC levels did not differ between groups. A degenerated disc can lead to locomotor defects as assessed by ladder and tail suspension tests, no pain signals in the von Frey test, upregulated matrix metalloproteinase-3, and downregulated aggrecan levels within the disc. Thus, we found that the DNA methylation status in the AF region of the disc was mainly changed after IDD and associated with aberrant TrpV1 expression in degenerated discs.<\/jats:p>","DOI":"10.3390\/cells11223547","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T02:07:48Z","timestamp":1668046068000},"page":"3547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Epigenetic Changes within the Annulus Fibrosus by DNA Methylation in Rat Intervertebral Disc Degeneration Model"],"prefix":"10.3390","volume":"11","author":[{"given":"Jin Young","family":"Hong","sequence":"first","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunseong","family":"Kim","sequence":"additional","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Jin","family":"Jeon","sequence":"additional","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junseon","family":"Lee","sequence":"additional","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhwan","family":"Yeo","sequence":"additional","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Hyuk","family":"Ha","sequence":"additional","affiliation":[{"name":"Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul 135-896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1136\/ard.2010.137836","article-title":"Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: The UK Twin Spine Study","volume":"70","author":"Livshits","year":"2011","journal-title":"Ann. 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