{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:12:33Z","timestamp":1788581553238,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471026"],"award-info":[{"award-number":["82471026"]}],"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":["82301030"],"award-info":[{"award-number":["82301030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2405901"],"award-info":[{"award-number":["2022YFC2405901"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Alveolar bone injury represents a prevalent clinical challenge in dentistry, for which stem cell\u2010based therapy has emerged as a promising strategy to promote bone regeneration. N\u2010acetylcysteine (NAC), a potent antioxidant, has been shown to modulate the PI3K\u2010AKT signalling pathway and potentially enhance osteogenesis; however, the specific downstream effectors mediating this process remain unidentified. In this study, post\u2010extraction serum metabolomic profiling revealed that alveolar bone injury is accompanied by systemic oxidative stress and metabolic remodelling. Transcriptomic analysis of antioxidant\u2010treated dental stem cells further identified type VI collagen A1 (COL6A1) as a key functional mediator. We subsequently investigated the role of COL6A1 in antioxidant\u2010mediated osteogenesis through immunofluorescence and protein assays, and performed knockdown and in\u00a0vivo experiments to evaluate its function in oxidative stress regulation and osteogenic differentiation. Our results demonstrated that alveolar bone injury is associated with systemic oxidative stress and global metabolic alterations. In\u00a0vitro, NAC markedly promoted the osteogenic differentiation of dental follicle stem cells (DFSCs) by activating the PI3K\u2010AKT pathway and upregulating COL6A1. COL6A1 knockdown resulted in elevated reactive oxygen species (ROS) levels, impaired mitochondrial function, and attenuated NAC\u2010mediated osteogenesis. In\u00a0vivo, NAC\u2010treated DFSCs exhibited enhanced bone healing and extracellular matrix (ECM) deposition in a rat model of alveolar bone injury, effects that were mediated through COL6A1 upregulation. Collectively, these findings demonstrate that NAC enhances osteogenesis in DFSCs via the PI3K\u2010AKT\u2010COL6A1 axis, offering a promising antioxidant\u2010based strategy for stem cell therapies in bone regeneration. Moreover, COL6A1 is essential for maintaining redox homeostasis and represents a potential therapeutic target for improving regenerative outcomes.<\/jats:p>","DOI":"10.1111\/cpr.70220","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T02:49:16Z","timestamp":1778208556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Collagen Type\n                    <scp>VI<\/scp>\n                    Alpha 1 as a Regulator of Redox Homeostasis in Antioxidant\u2010Enhanced Osteogenesis of Dental Stem Cells"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8977-8446","authenticated-orcid":false,"given":"Zhaosong","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Tianjin Medical University School and Hospital of Stomatology, Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin People's Republic of China"},{"name":"Department of Geriatric Dentistry, Beijing Laboratory of Biomedical Materials Peking University School and Hospital of Stomatology  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruimeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin People's Republic of 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School and Hospital of Stomatology, Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuling","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2933-2207","authenticated-orcid":false,"given":"Lizhi","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), School of Basic Medical Science Tianjin Medical University  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sui","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Tianjin Medical University School and Hospital of Stomatology, Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration Tianjin Medical University Institute of Stomatology  Tianjin People's Republic of 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