{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:20:20Z","timestamp":1790821220008,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"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":["32071246"],"award-info":[{"award-number":["32071246"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Program of Science and Technology in Xi\u2019an City","award":["23YXYJ0127"],"award-info":[{"award-number":["23YXYJ0127"]}]},{"name":"Basic Scientific Research Funds of Xi\u2019an Jiaotong University","award":["xzy022023079"],"award-info":[{"award-number":["xzy022023079"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>This study investigates the mechanisms underlying osteocyte injury in a high glucose (HG) environment and explores potential therapeutic targets and diagnostic markers for diabetic osteoporosis, a common complication of type 2 diabetes mellitus (T2DM). Hyperglycemia induces oxidative stress through the reactive oxygen species (ROS) production, which impair osteocytes and accelerate bone loss. To examine these effects, MLO-Y4 cells and primary mouse osteocytes were cultured under normal glucose and HG conditions, with additional treatments using N-acetylcysteine (NAC, ROS scavenger) and rapamycin (autophagy promoter and mTOR inhibitor). Cell viability, ROS levels, and the autophagy and apoptosis markers expression (Beclin1, LC3, p62, Bax, Bcl2, cytochrome C, and caspase3) were assessed using CCK8\/ATP level assay, flow cytometry, Western blot, qRT-PCR, immunofluorescence, and TUNEL staining. The results showed that HG inhibits cell proliferation, induces insulin resistance, generates ROS, alters antioxidant enzymes, and promotes oxidative stress, leading to mTOR activation, subsequent autophagy inhibition, and osteocyte apoptosis. NAC mitigated these effects, while rapamycin prevented HG-induced apoptosis by inhibiting mTOR activation and promoting autophagy. This suggests that ROS-induced mTOR activation impairs autophagy and hinders the clearance of damaged osteocytes, triggering apoptosis. This research provides foundational evidence and novel insights into diabetic osteoporosis pathogenesis and potential therapies.<\/jats:p>","DOI":"10.3390\/antiox14111306","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:23:59Z","timestamp":1761873839000},"page":"1306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Reactive Oxygen Species (ROS) Drive Osteocyte Dysfunction in Diabetic Osteoporosis by Impairing Autophagy and \r\nTriggering Apoptosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Mengqi","family":"Han","sequence":"first","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"},{"name":"Laboratory Center of Stomatology, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"},{"name":"Laboratory Center of Stomatology, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"},{"name":"Laboratory Center of Stomatology, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengying","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"},{"name":"Laboratory Center of Stomatology, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"},{"name":"Laboratory Center of Stomatology, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"},{"name":"Laboratory Center of Stomatology, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongbo","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"},{"name":"Laboratory Center of Stomatology, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1359\/jbmr.081207","article-title":"Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications","volume":"24","author":"Yamamoto","year":"2009","journal-title":"J. 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