Hypoxia Exacerbates Rat Periodontitis By Hif-1Α - Mettl3 Signaling Axis

Hypoxia plays a pivotal role in the progression of periodontitis; however, the underlying mechanism remains elusive. In this study, RAW 264.7 cells were cultured and a rat model of ligation-induced periodontitis was established under hypoxic conditions. HE staining, TRAP staining, immunofluorescence, western blotting, and micro-computed tomography (CT) were used to observe the role of hypoxia in periodontitis and elucidate the relevant mechanisms. Hypoxia remarkably aggravated periodontal inflammatory infiltration and alveolar bone resorption. Micro-CT analysis revealed that the reduction of avleoar bone in the Periodototis+Hypoxia(P+H) group was significantly greater than that observed in the Periodototis (P) group. A large number of CD68- and CD11b-positive inflammatory cells, as well as TRAP- and cathepsin K(CTSK)-positive osteoclasts were observed. In vitro experiments showed that a hypoxic environment significantly upregulated the expression of Hif-1α and METTL3. Co-localization of Hif-1α and METTL3 was observed in the nuclei of Raw246.7 macrophages. Multicolor immunofluorescence staining revealed that Hif-1α, METTL3, and CTSK were co-localized within the osteoclasts in rat periodontitis. In conclusion, hypoxia exacerbates periodontitis in rats through the Hif-1α - METTL3 signaling axis. This signaling axis could be a potential intervention target for periodontal treatment, providing novel insights into the development of therapeutic strategies for periodontal diseases.