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Hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), a key transcriptional regulator, is stabilized under the hypoxic conditions associated with pulpitis. This review examines the roles and molecular mechanisms of HIF-1\u03b1 in the pathogenesis and progression of pulpitis. Hypoxia in pulpitis prevents the degradation of HIF-1\u03b1, leading to its elevated expression. Furthermore, lipopolysaccharide from invading bacteria upregulates HIF-1\u03b1 transcription through nuclear factor kappa B and mitogen-activated protein kinase pathways. HIF-1\u03b1 regulates immunity and pulp remodeling in a stage-dependent manner by controlling various cytokines. During the inflammation stage, HIF-1\u03b1 promotes recruitment of neutrophils and enhances their bactericidal effects by facilitating neutrophil extracellular trap release and M1 macrophage polarization. Concurrently, HIF-1\u03b1 contributes to programmed cell death by increasing mitophagy. In the proliferation stage, HIF-1\u03b1 stimulates immune responses involving T cells and dendritic cells. In the remodeling stage, HIF-1\u03b1 supports angiogenesis and pulp-dentin regeneration. However, excessive pulpitis-induced hypoxia may disrupt vascular dynamics within the pulp chamber. This disruption highlights a critical threshold for HIF-1\u03b1, beyond which its effects might accelerate pulp necrosis. Overall, HIF-1\u03b1 plays a central role in regulating immunity and tissue remodeling during pulpitis. A comprehensive understanding of the physiological and pathological roles of HIF-1\u03b1 is essential for the advancement of effective strategies to manage irreversible pulpitis.<\/jats:p>","DOI":"10.1177\/00220345251320970","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:33:06Z","timestamp":1742344386000},"page":"715-724","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["The Roles and Molecular Mechanisms of HIF-1\u03b1 in Pulpitis"],"prefix":"10.1177","volume":"104","author":[{"given":"L.","family":"Shao","sequence":"first","affiliation":[{"name":"Capital Medical University School of Stomatology, Beijing, China"},{"name":"School of Basic Medical Sciences, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, Peking 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