{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:24:11Z","timestamp":1788351851947,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","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":"publisher","award":["32472983"],"award-info":[{"award-number":["32472983"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32472987"],"award-info":[{"award-number":["32472987"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32472983"],"award-info":[{"award-number":["32472983"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32472987"],"award-info":[{"award-number":["32472987"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>As the only mammalian appendage capable of complete regeneration, deer antlers serve as an invaluable model to investigate cartilage regrowth, but the underlying mechanism remains unclear. This study revealed that addition of palmitic acid (PA), an abundant long-chain saturated free fatty acid, inhibited the proliferation and hypertrophy of antler chondrocytes while promoting chondrocyte apoptosis. PA treatment activated NOTCH1 signaling and restrained the transport of Ca2+ from the cytosol to the endoplasmic reticulum (ER) via RBPJ (recombination signal-binding protein for immunoglobulin kappa J region)-targeted TMTC4 (transmembrane O-mannosyltransferase targeting cadherins 4), resulting in a reduction in ER Ca2+. Meanwhile, PA disrupted the structure and function of mitochondria-associated ER membranes (MAMs) via TGM2 (transglutaminase 2) through the cytosolic Ca2+-mediated PPP3CB (protein phosphatase 3 catalytic subunit beta)-NFATC2 (nuclear factor of activated T cells cytoplasmic 2) pathway. Further analysis demonstrated that PA induced mitochondrial dysfunction via MAM-mediated mitochondrial Ca2+ insufficiency, thereby restricting mitophagy and attenuating lysosomal acidification. This caused the leakage of mitochondrial reactive oxygen species (mtROS) from depolarized mitochondria into the cytosol via the mitochondrial permeability transition pore, thereby inducing lipid peroxidation, while the addition of ROS scavengers prevented the negative effects of chondrocyte proliferation and hypertrophy and protected chondrocytes from apoptosis in the context of PA. Collectively, PA treatment regulated the proliferation, apoptosis and hypertrophy of antler chondrocytes by disrupting MAM function.<\/jats:p>","DOI":"10.3390\/antiox15091108","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:04:16Z","timestamp":1788350656000},"page":"1108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Palmitic Acid Inhibits the Proliferation and Hypertrophy of Antler Chondrocytes by Disrupting Mitochondria-Associated Endoplasmic Reticulum Membrane Function"],"prefix":"10.3390","volume":"15","author":[{"given":"Qiaoling","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Zhanqing","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Xueyuan","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Yinfei","family":"Xing","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Chenhao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Baiyu","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Zhanpeng","family":"Yue","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Bin","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","first-page":"57","article-title":"New physiological insights into the phenomena of deer antler: A unique model for skeletal tissue regeneration","volume":"27","author":"Feleke","year":"2020","journal-title":"J. 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