{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:57:47Z","timestamp":1787684267423,"version":"build-2784847793"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,3,3]],"date-time":"2024-03-03T00:00:00Z","timestamp":1709424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Bone defects are characterized by a hypoxic environment, which affects bone tissue repair. However, the role of hypoxia in the repair of alveolar bone defects remains unclear. Human periodontal ligament stem cells (hPDLSCs) are high\u2010quality seed cells for repairing alveolar bone defects, whose behavior changes under hypoxia. However, their mechanism of action is not known and needs to be elucidated. We hypothesized that hypoxia might be beneficial to alveolar bone defect repair and the osteogenic differentiation of hPDLSCs. To test this hypothesis, cobalt chloride (CoCl\n                    <jats:sub>2<\/jats:sub>\n                    ) was used to create a hypoxic environment, both in vitro and in vivo. In vitro study, the best osteogenic effect was observed after 48\u2009h of hypoxia in hPDLSCs, and the AKT\/mammalian target of rapamycin\/eukaryotic translation initiation factor 4e\u2010binding protein 1 (AKT\/mTOR\/4EBP\u20101) signaling pathway was significantly upregulated. Inhibition of the AKT\/mTOR\/4EBP\u20101 signaling pathway decreased the osteogenic ability of hPDLSCs under hypoxia and hypoxia\u2010inducible factor 1 alpha (HIF\u20101\u03b1) expression. The inhibition of HIF\u20101\u03b1 also decreased the osteogenic capacity of hPDLSCs under hypoxia without significantly affecting the level of phosphorylation of AKT\/mTOR\/4EBP\u20101. In vitro study, Micro\u2010CT and tissue staining results show better bone regeneration in hypoxic group than control group. These results suggested that hypoxia promoted alveolar bone defect repair and osteogenic differentiation of hPDLSCs, probably through AKT\/mTOR\/4EBP\u20101\/HIF\u20101\u03b1 signaling. These findings provided important insights into the regulatory mechanism of hypoxia in hPDLSCs and elucidated the effect of hypoxia on the healing of alveolar bone defects. This study highlighted the importance of physiological oxygen conditions for tissue engineering.\n                  <\/jats:p>","DOI":"10.1002\/cbin.12148","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T02:19:05Z","timestamp":1709518745000},"page":"808-820","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["CoCl\n                    <sub>2<\/sub>\n                    \u2010Induced hypoxia promotes hPDLSCs osteogenic differentiation through AKT\/mTOR\/4EBP\u20101\/HIF\u20101\u03b1 signaling and facilitates the repair of alveolar bone defects"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2523-7850","authenticated-orcid":false,"given":"Zhibo","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatological Hospital Southwest Medical University Luzhou China"},{"name":"Luzhou Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration The Affiliated Stomatological Hospital of Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatological Hospital Southwest Medical University Luzhou China"},{"name":"Luzhou Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration The Affiliated Stomatological Hospital of Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatological Hospital Southwest Medical University Luzhou China"},{"name":"Luzhou Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration The Affiliated Stomatological Hospital of Southwest Medical University Luzhou 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