Substance P aggravates periodontitis by upregulating HIF-1 α and RANKL / OPG ratio

Abstract Background Both substance P (SP) and hypoxia-inducible factor 1 alpha (HIF-1α) get involved in inflammation and angiogenesis. But the interrelation between SP and HIF-1α in rat periodontitis is still little known. Methods Ligation‐induced rat periodontitis was established to observe the expression of SP and HIF-1α by immunohistochemistry. Gingival fibroblasts and bone marrow macrophages (BMMs) were respectively cultured and stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). 10 nM SP with or without 1µg/ml LPS was added to elaborate the relationship between SP and HIF-1α in gingival fibroblasts. The effect of SP on osteoclastogenesis was tested by TRAP staining. Western blotting was applied to investigate the expressions of HIF-1α, osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL). Results The expression levels of HIF-1α and SP were higher in periodontitis than normal tissues. SP could upregulate the level of HIF-1α and RANKL/OPG ratio in LPS-stimulated gingival fibroblasts. SP with or without LPS also facilitated RANKL induced osteoclastogenesis. Conclusion Substance P aggravates periodontitis by increasing HIF-1α and RANKL / OPG ratio.