Abstract
BackgroundBoth substance P and hypoxia-inducible factor 1 alpha (HIF-1α) are involved in inflammation and angiogenesis. However, the relationship between substance P and HIF-1α in rat periodontitis is still unknown.MethodsLigation-induced rat periodontitis was established to observe the distribution and expression of substance P and HIF-1α by immunohistochemistry. Rat gingival fibroblasts were cultured and stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). Recombinant substance P was applied to elaborate the relationship between substance P and HIF-1α in gingival fibroblasts in vitro. Primary mouse bone marrow-derived macrophages (BMMs) were isolated and cultured to observe the effect of substance P on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis by TRAP staining. Western blotting was used to investigate the expression of HIF-1α, osteoprotegerin (OPG) and RANKL.ResultsRat experimental periodontitis was successfully established 6 weeks after ligation. Gingival inflammatory infiltration and alveolar bone loss were observed. Positive expression of substance P was found in the infiltrating cells. Higher HIF-1α levels were observed in periodontitis compared to that of normal tissues. Substance P upregulated the level of HIF-1α in gingival fibroblasts with or without 1 μg/ml LPS in vitro (*P < 0.05). Substance P upregulated the expression of HIF-1α in RANKL-stimulated BMMs in vitro. Substance P also increased the RANKL/OPG ratio in gingival fibroblasts (*P < 0.05). Both 10 nM and 50 nM substance P promoted RANKL-induced osteoclast differentiation (*P < 0.05).ConclusionSubstance P participates in periodontitis by upregulating HIF-1α and the RANKL/OPG ratio.
Highlights
Both substance P and hypoxia-inducible factor 1 alpha (HIF-1α) are involved in inflammation and angiogenesis
Western blotting showed that the gingiva in periodontitis expressed higher Hypoxia-inducible factor-1 alpha (HIF-1α) compared with that of normal gingiva (*P < 0.05) (Fig. 2d)
Substance P upregulated the level of HIF-1α in gingival fibroblasts After 24 h, both 1 μg/ml LPS and 10 nM substance P obviously induced TNF-α expression (*P < 0.05) (Fig. 4a)
Summary
Both substance P and hypoxia-inducible factor 1 alpha (HIF-1α) are involved in inflammation and angiogenesis. Substance P is closely related to neurogenic inflammation and plays a key role in the immune system by regulating the proliferation, migration and activation of immune cells [3]. A number of studies have shown that substance P, which is involved in inflammatory responses [4], exerts certain regulatory functions, such as increasing vascular permeability, affecting vasodilation [5, 6], and. In cellular responses to hypoxia, HIF-1α plays a key role [12]. Research has shown that HIF-1α plays a crucial role in physiological and pathophysiological angiogenesis by regulating vascular endothelial growth factor (VEGF) [13, 14]
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