{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T08:32:00Z","timestamp":1793003520067,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&D Project of China","award":["2023YFD1801100"],"award-info":[{"award-number":["2023YFD1801100"]}]},{"name":"Applied Basic Research Project of Shanxi Province","award":["202203021212434"],"award-info":[{"award-number":["202203021212434"]}]},{"name":"Applied Basic Research Project of Shanxi Province","award":["202403021211193"],"award-info":[{"award-number":["202403021211193"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32072934"],"award-info":[{"award-number":["32072934"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Project Supported by Shanxi Scholarship Council of China","award":["2022-101"],"award-info":[{"award-number":["2022-101"]}]},{"name":"Earmarked Fund for Modern Agro-industry Technology Research System of Shanxi Province","award":["2022-2025"],"award-info":[{"award-number":["2022-2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Long-term excessive fluoride intake from food causes skeletal fluorosis, which manifests as bone sclerosis, deformation, joint dysfunction, and even disability. Mitophagy and ion homeostasis regulate bone function. This study investigated the role of melatonin (MLT) in mitigating this condition, given its known involvement in bone remodeling and the fact that fluoride impairs its synthesis in the pineal gland. Firstly, network pharmacology and molecular docking identified mitophagy as MLT\u2019s key pathway against sodium fluoride (NaF)-induced osteosclerosis. Subsequently, a 400 mg\/kg\/day body weight NaF exposure model in chicken model with 25 mg\/kg\/day body weight MLT intervention were established in the current study. Fluoride exposure caused the disturbance of ion homeostasis, and the impairment of mitochondria and activation of PTEN-induced putative kinase1 (PINK1)\/E3 ubiquitin ligase Park2 (Parkin)-mediated mitophagy in the bone. Importantly, these deleterious effects were significantly restored by MLT supplementation. In conclusion, NaF causes bone injury via ion homeostasis disruption, osteoblast mitochondrial damage, leading to excessive mitophagy. MLT inhibits fluoride-induced mitophagy through the calcium ion flow-mediated PINK1\/Parkin pathway, mitigating bone damage. This study can not only ensure the safety of animal-derived food but also provide a theoretical basis for the prevention and treatment of fluorosis in humans and animals.<\/jats:p>","DOI":"10.3390\/foods14244173","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T13:17:07Z","timestamp":1764940627000},"page":"4173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Melatonin Supplementation Relieves Fluoride-Induced Bone Injury via Ion Homeostasis Disorder and PINK1\/Parkin-Mediated Mitophagy"],"prefix":"10.3390","volume":"14","author":[{"given":"Cuicui","family":"Zhuang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinying","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiguang","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Pei","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8375-5091","authenticated-orcid":false,"given":"Yangfei","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6005-8376","authenticated-orcid":false,"given":"Jianhai","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Naturally occurring organohalogen compounds\u2014A comprehensive review","volume":"121","author":"Gribble","year":"2023","journal-title":"Prog. 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