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It profoundly affects oral health, esthetics, and masticatory function and is increasingly recognized as a contributing risk factor for systemic disorders. Deep periodontal pockets establish a severely hypoxic microenvironment induced by periodontal pathogens, increased oxygen consumption of infiltrated inflammatory cells, and accompanying periodontal vascular changes. The cellular response to hypoxia is centrally regulated by hypoxia-inducible factor 1 alpha (HIF-1\u03b1), which is also recognized as a critical factor driving the progression of periodontal tissue destruction. In vivo and in vitro studies have shown the upregulation of HIF-1\u03b1 in both animal periodontitis models and clinical samples from individuals with periodontitis, where its expression correlates positively with deteriorating clinical periodontal parameters. Experimental and clinical studies using mouse conditional knockout models, selective small-molecule inhibitors, and human-derived materials have demonstrated clear causal roles for hypoxia-driven HIF-1\u03b1 signaling in the progression of periodontitis. This conclusion is supported by mechanistic evidence demonstrating that HIF-1\u03b1 induces aberrant neovascularization, enhances osteoclastogenesis leading to subsequent alveolar bone resorption, and promotes M1 macrophage polarization along with proinflammatory cytokine production. Hypoxia, via HIF-1\u03b1, synergistically acts with periodontal pathogens to amplify periodontal inflammation and oxidative stress, driving persistent extracellular matrix destruction in periodontal tissues. This critical review summarizes recent findings, using in vitro and in vivo approaches using animal and human-derived materials, on the role of hypoxia, primarily through the HIF-1\u03b1 pathway, in periodontitis pathogenesis as well as the potential of hypoxia-based strategies and targeted modulation of HIF-1\u03b1 signaling through HIF-1\u03b1 stabilizers for managing periodontitis and promoting periodontal regeneration, while highlighting the existing gaps in our understanding and the limitations of current research, which can serve as a foundation for guiding future studies in this area.<\/jats:p>","DOI":"10.1177\/00220345261426978","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T04:10:02Z","timestamp":1773893402000},"page":"707-716","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["The Contribution of the Hypoxia Inducible Factor-1\u03b1 Axis to Periodontitis"],"prefix":"10.1177","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4231-429X","authenticated-orcid":false,"given":"A.","family":"Fadl","sequence":"first","affiliation":[{"name":"College of Dentistry, University of Saskatchewan, Saskatoon, SK, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2832-283X","authenticated-orcid":false,"given":"A.","family":"Leask","sequence":"additional","affiliation":[{"name":"College of Dentistry, University of Saskatchewan, Saskatoon, SK, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Afacan B et al. 2019. Gingival crevicular fluid and salivary HIF-1\u03b1 VEGF and TNF-\u03b1 levels in periodontal health and disease. J Periodontol. 90(7):788\u2013797. https:\/\/doi.org\/10.1002\/jper.18-0412","DOI":"10.1002\/JPER.18-0412"},{"key":"e_1_3_2_3_1","doi-asserted-by":"crossref","unstructured":"Balci Yuce H Karatas \u00d6 Tulu F Altan A Gevrek F. 2019. Effect of diabetes on collagen metabolism and hypoxia in human gingival tissue: a stereological histopathological and immunohistochemical study. Biotech Histochem. 94(1):65\u201373. https:\/\/doi.org\/10.1080\/10520295.2018.1508745","DOI":"10.1080\/10520295.2018.1508745"},{"key":"e_1_3_2_4_1","doi-asserted-by":"crossref","unstructured":"Bengtsson VW Persson GR Berglund JS Renvert S. 2021. Periodontitis related to cardiovascular events and mortality: a long-time longitudinal study. 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