P 物质通过上调 HIF-1α 和 RANKL/OPG 比值参与牙周炎的发生。
Substance P participates in periodontitis by upregulating HIF-1α and RANKL/OPG ratio.
机构信息
Department of Periodontology, School and Hospital of Stomatology, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, 250012, Jinan, Shandong, People's Republic of China.
Department of Endodontics, Jinan Stomatological Hospital, Jinan, Shandong, People's Republic of China.
出版信息
BMC Oral Health. 2020 Jan 30;20(1):27. doi: 10.1186/s12903-020-1017-9.
BACKGROUND
Both 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.
METHODS
Ligation-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.
RESULTS
Rat 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).
CONCLUSION
Substance P participates in periodontitis by upregulating HIF-1α and the RANKL/OPG ratio.
背景
P 物质和缺氧诱导因子 1α（HIF-1α）都参与了炎症和血管生成。然而，P 物质和 HIF-1α 在大鼠牙周炎中的关系尚不清楚。
方法
通过免疫组织化学观察结扎诱导的大鼠牙周炎中 P 物质和 HIF-1α的分布和表达。培养大鼠牙龈成纤维细胞，用牙龈卟啉单胞菌脂多糖（LPS）刺激。应用重组 P 物质阐述 P 物质与牙龈成纤维细胞中 HIF-1α的关系。分离培养原代小鼠骨髓来源巨噬细胞（BMMs），通过 TRAP 染色观察 P 物质对核因子-κB 受体激活剂配体（RANKL）诱导破骨细胞生成的影响。Western blot 用于研究 HIF-1α、骨保护素（OPG）和 RANKL 的表达。
结果
结扎后 6 周成功建立大鼠实验性牙周炎。观察到牙龈炎症浸润和牙槽骨丢失。发现浸润细胞中有 P 物质的阳性表达。与正常组织相比，牙周炎组织中 HIF-1α水平升高。P 物质在体外无论有无 1μg/ml LPS 均可上调牙龈成纤维细胞中 HIF-1α的水平（*P<0.05）。P 物质在体外上调 RANKL 刺激的 BMMs 中 HIF-1α的表达。P 物质还增加了牙龈成纤维细胞中 RANKL/OPG 比值（*P<0.05）。10nM 和 50nM 的 P 物质均促进 RANKL 诱导的破骨细胞分化（*P<0.05）。
结论
P 物质通过上调 HIF-1α和 RANKL/OPG 比值参与牙周炎的发生。
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