{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T06:43:52Z","timestamp":1772001832144,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The origin of intervertebral disc degeneration (IDD) is highly complex, where both cartilage endplate remodeling and vertebral osteoporosis are of utmost importance. Myristic acid (MA), a saturated fatty acid derived from nutmeg, a traditional Chinese herb, has been shown to boost memory. Additionally, its isomers have been verified to have anti-osteoporotic characteristics. However, the precise mechanism by which MA functions in relation to IDD remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>In vivo<\/jats:italic>, a naturally aged animal model was used. The drug\u2014administration method of MA was intraperitoneal injection to mice aged 22\u00a0months at a dose of 2\u00a0mg\/kg\u00b7d for 2\u00a0months. Micro-CT observed vertebral bone mass and endplate changes, followed by Hematoxylin\u2012eosin (H&amp;amp;E), Masson, and Safranin-O staining of tissues. TRAP staining counted osteoclasts; immunohistochemistry detected the expressions of Aggrecan and Collagen II. Bioinformatics explored MA\u2019s anti-IDD mechanism. <jats:italic>In vitro<\/jats:italic>, MA-treated senescent endplate chondrocytes (induced by TBHP) were analyzed by RT-qPCR and immunofluorescence (IF) for senescence and matrix synthesis markers. TRAP and F-actin detected MA\u2019s effect on RAW264.7 osteoclast differentiation (induced by RANKL); qPCR examined the expressions of osteoclast genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using the naturally aged model, we found that MA tended to improve vertebral osteoporosis and endplate osteochondral remodeling, decreased the TRAP activity of the endplate, and alleviated IDD in naturally aged mice. Bioinformatics analysis suggested that the relationships among IDD, osteoporosis, and endplate degeneration were mainly linked to cellular senescence. <jats:italic>In vitro<\/jats:italic>, MA postponed the senescence of TBHP-induced endplate chondrocytes by increasing the expression of Aggrecan and decreasing the expressions of MMP-3, MMP-9, and the senescence markers p16 and p21. Additionally, MA notably inhibited osteoclast activity, as evidenced by a decrease in the number of osteoclasts and a significant suppression of F-actin formation. At the molecular level, MA efficiently reduced the expressions of osteoclast marker genes like ACP-5, CTSK, and DC-STAMP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings of this research suggest that MA is capable of inhibiting endplate osteochondral remodeling and vertebral osteoporosis, diminishing osteoclastogenesis to preserve bone mass, and consequently delaying IDD in naturally aged mice. Hence, MA holds the potential to serve as an alternative therapeutic approach for IDD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1517221","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T13:32:16Z","timestamp":1744378336000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Myristic acid beneficially modulates intervertebral disc degeneration by preventing endplate osteochondral remodeling and vertebral osteoporosis in naturally aged mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Yan","family":"Gong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingda","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zelin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weicheng","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanchi","family":"Gan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahui","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jizhi","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guifeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Shang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honglin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gengyang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobing","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaojun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"R152","DOI":"10.1186\/ar3103","article-title":"Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis","volume":"12","author":"Bellido","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"B2","doi-asserted-by":"publisher","first-page":"924918","DOI":"10.3389\/fbioe.2022.924918","article-title":"Raloxifene stimulates estrogen signaling to protect against age- and sex-related intervertebral disc degeneration in mice","volume":"10","author":"Bhadouria","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"609","DOI":"10.3390\/foods11040609","article-title":"Effect of dietary palm kernel oil on the quality, fatty acid profile, and sensorial attributes of young bull meat","volume":"11","author":"Dos Santos","year":"2022","journal-title":"Foods"},{"key":"B4","doi-asserted-by":"publisher","first-page":"S46","DOI":"10.1093\/neuros\/nyw078","article-title":"Intervertebral disk degeneration and repair","volume":"80","author":"Dowdell","year":"2017","journal-title":"Neurosurgery"},{"key":"B5","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.gendis.2016.04.005","article-title":"Genetic factors in intervertebral disc degeneration","volume":"3","author":"Feng","year":"2016","journal-title":"Genes. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"119324","DOI":"10.1016\/j.lfs.2021.119324","article-title":"Chlorogenic Acid retards cartilaginous endplate degeneration and ameliorates intervertebral disc degeneration via suppressing NF-\u03baB signaling","volume":"274","author":"Ge","year":"2021","journal-title":"Life Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2356","DOI":"10.1016\/S0140-6736(18)30480-X","article-title":"What low back pain is and why we need to pay attention","volume":"391","author":"Hartvigsen","year":"2018","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3109\/03008208109152130","article-title":"Nutrition of the intervertebral disc: solute transport and metabolism","volume":"8","author":"Holm","year":"1981","journal-title":"Connect. Tissue Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/S0140-6736(21)00733-9","article-title":"Low back pain","volume":"398","author":"Knezevic","year":"2021","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.ejphar.2015.10.053","article-title":"Myristoleic acid inhibits osteoclast formation and bone resorption by suppressing the RANKL activation of Src and Pyk2","volume":"768","author":"Kwon","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.molmed.2022.07.007","article-title":"Epigenetic regulation in intervertebral disc degeneration","volume":"28","author":"Li","year":"2022","journal-title":"Trends Mol. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1007\/s00198-023-06880-x","article-title":"Does vertebral osteoporosis delay or accelerate lumbar disc degeneration? A systematic review","volume":"34","author":"Li","year":"2023","journal-title":"Osteoporos. Int."},{"key":"B13","doi-asserted-by":"publisher","first-page":"eadg8982","DOI":"10.1126\/scitranslmed.adg8982","article-title":"Parathyroid hormone treatment partially reverses endplate remodeling and attenuates low back pain in animal models of spine degeneration","volume":"15","author":"Ling","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1186\/s12891-015-0788-7","article-title":"Protective effect of calcitonin on lumbar fusion-induced adjacent-segment disc degeneration in ovariectomized rat","volume":"16","author":"Liu","year":"2015","journal-title":"BMC Musculoskelet. Disord."},{"key":"B15","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/j.bone.2013.03.002","article-title":"Alendronate retards the progression of lumbar intervertebral disc degeneration in ovariectomized rats","volume":"55","author":"Luo","year":"2013","journal-title":"Bone"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1007\/s00586-014-3333-8","article-title":"Vertebral endplate change as a feature of intervertebral disc degeneration: a heritability study","volume":"23","author":"M\u00e4\u00e4tt\u00e4","year":"2014","journal-title":"Eur. Spine J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.mehy.2013.01.030","article-title":"Osteoporosis delays intervertebral disc degeneration by increasing intradiscal diffusive transport of nutrients through both mechanical and vascular pathophysiological pathways","volume":"80","author":"Mattei","year":"2013","journal-title":"Med. Hypotheses"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e1164","DOI":"10.1002\/jsp2.1164","article-title":"Development of a standardized histopathology scoring system using machine learning algorithms for intervertebral disc degeneration in the mouse model\u2014an ORS spine section initiative","volume":"4","author":"Melgoza","year":"2021","journal-title":"JOR Spine"},{"key":"B19","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3390\/ijms24010208","article-title":"Discogenic low back pain: anatomy, pathophysiology and treatments of intervertebral disc degeneration","volume":"24","author":"Mohd Isa","year":"2022","journal-title":"IJMS"},{"key":"B20","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1136\/annrheumdis-2020-219515","article-title":"Tissue physiology revolving around the clock: circadian rhythms as exemplified by the intervertebral disc","volume":"80","author":"Morris","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/nrm3902","article-title":"Extracellular matrix assembly: a multiscale deconstruction","volume":"15","author":"Mouw","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s007740300004","article-title":"Correlation between bone mineral density and intervertebral disk degeneration in pre- and postmenopausal women","volume":"21","author":"Nanjo","year":"2003","journal-title":"J. Bone Mineral Metabolism"},{"key":"B23","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1007\/s00586-006-0220-y","article-title":"Biological treatment strategies for disc degeneration: potentials and shortcomings","volume":"16","author":"Paesold","year":"2007","journal-title":"Eur. Spine J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e13442","DOI":"10.1111\/acel.13442","article-title":"Neutralization of oxidized phospholipids attenuates age\u2010associated bone loss in mice","volume":"20","author":"Palmieri","year":"2021","journal-title":"Aging Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1097\/BRS.0000000000002352","article-title":"Vertebral endplate defect as initiating factor in intervertebral disc degeneration: strong association between endplate defect and disc degeneration in the general population","volume":"43","author":"Rade","year":"2018","journal-title":"Spine"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.22603\/ssrr.2017-0095","article-title":"Molecular mechanisms of intervertebral disc degeneration","volume":"3","author":"Rider","year":"2019","journal-title":"Spine Surg. Relat. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"907526","DOI":"10.3389\/fnut.2022.907526","article-title":"Myristic acid alleviates hippocampal aging correlated with GABAergic signaling","volume":"9","author":"Shang","year":"2022","journal-title":"Front. Nutr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.matbio.2018.02.025","article-title":"Glycosaminoglycan synthesis in the nucleus pulposus: dysregulation and the pathogenesis of disc degeneration","volume":"71","author":"Silagi","year":"2018","journal-title":"Matrix Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"686","DOI":"10.3390\/biom13040686","article-title":"Cellular senescence in intervertebral disc aging and degeneration: molecular mechanisms and potential therapeutic opportunities","volume":"13","author":"Silwal","year":"2023","journal-title":"Biomolecules"},{"key":"B30","doi-asserted-by":"publisher","first-page":"6612","DOI":"10.3390\/ijms23126612","article-title":"Current perspectives on nucleus pulposus fibrosis in disc degeneration and repair","volume":"23","author":"Sun","year":"2022","journal-title":"IJMS"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1016\/j.joca.2017.01.001","article-title":"Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study","volume":"25","author":"Teraguchi","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"B32","doi-asserted-by":"publisher","first-page":"122162","DOI":"10.1016\/j.lfs.2023.122162","article-title":"Activation of the Nrf-2 pathway by pinocembrin safeguards vertebral endplate chondrocytes against apoptosis and degeneration caused by oxidative stress","volume":"333","author":"Wang","year":"2023","journal-title":"Life Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.intimp.2019.01.004","article-title":"Ligustilide alleviated IL-1\u03b2 induced apoptosis and extracellular matrix degradation of nucleus pulposus cells and attenuates intervertebral disc degeneration in vivo","volume":"69","author":"Wang","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"551","DOI":"10.21037\/qims.2018.07.04","article-title":"Senile osteoporosis is associated with disc degeneration","volume":"8","author":"W\u00e1ng","year":"2018","journal-title":"Quant. Imaging Med. Surg."},{"key":"B35","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/s41419-017-0151-z","article-title":"Prolactin inhibits the progression of intervertebral disc degeneration through inactivation of the NF-\u03baB pathway in rats","volume":"9","author":"Wu","year":"2018","journal-title":"Cell Death Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/s13075-018-1701-1","article-title":"Osteoporosis of the vertebra and osteochondral remodeling of the endplate causes intervertebral disc degeneration in ovariectomized mice","volume":"20","author":"Xiao","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"B37","doi-asserted-by":"publisher","first-page":"110159","DOI":"10.1016\/j.intimp.2023.110159","article-title":"Astaxanthin suppresses oxidative stress and calcification in vertebral cartilage endplate via activating Nrf-2\/HO-1 signaling pathway","volume":"119","author":"Yang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1016\/j.spinee.2015.01.026","article-title":"Establishment of intervertebral disc degeneration model induced by ischemic sub-endplate in rat tail","volume":"15","author":"Yuan","year":"2015","journal-title":"Spine J."},{"key":"B39","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1186\/s12891-023-06891-z","article-title":"Potential molecular targets and drugs for basement membranes-related intervertebral disk degeneration through bioinformatics analysis and molecular docking","volume":"24","author":"Zhou","year":"2023","journal-title":"BMC Musculoskelet. Disord."},{"key":"B40","doi-asserted-by":"publisher","first-page":"113117","DOI":"10.1016\/j.jep.2020.113117","article-title":"The treatment of intervertebral disc degeneration using Traditional Chinese Medicine","volume":"263","author":"Zhu","year":"2020","journal-title":"J. Ethnopharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1517221\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T13:32:17Z","timestamp":1744378337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1517221\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,1]]},"references-count":40,"alternative-id":["10.3389\/fphar.2025.1517221"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1517221","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,1]]},"article-number":"1517221"}}