The Roles and Molecular Mechanisms of HIF-1α in Pulpitis.

Abstract

Pulpitis is characterized by inflammation within dental pulp tissue, primarily triggered by bacterial infection. Hypoxia-inducible factor-1α (HIF-1α), a key transcriptional regulator, is stabilized under the hypoxic conditions associated with pulpitis. This review examines the roles and molecular mechanisms of HIF-1α in the pathogenesis and progression of pulpitis. Hypoxia in pulpitis prevents the degradation of HIF-1α, leading to its elevated expression. Furthermore, lipopolysaccharide from invading bacteria upregulates HIF-1α transcription through nuclear factor kappa B and mitogen-activated protein kinase pathways. HIF-1α regulates immunity and pulp remodeling in a stage-dependent manner by controlling various cytokines. During the inflammation stage, HIF-1α promotes recruitment of neutrophils and enhances their bactericidal effects by facilitating neutrophil extracellular trap release and M1 macrophage polarization. Concurrently, HIF-1α contributes to programmed cell death by increasing mitophagy. In the proliferation stage, HIF-1α stimulates immune responses involving T cells and dendritic cells. In the remodeling stage, HIF-1α 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-1α, beyond which its effects might accelerate pulp necrosis. Overall, HIF-1α plays a central role in regulating immunity and tissue remodeling during pulpitis. A comprehensive understanding of the physiological and pathological roles of HIF-1α is essential for the advancement of effective strategies to manage irreversible pulpitis.