Temporal and spatial effects on C-reactive protein's regulation of inducible nitric oxide synthase production in periodontal disease
Temporal and spatial effects on C-reactive protein's regulation of inducible nitric oxide synthase production in periodontal disease
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DOI：
10.1002/jper.22-0529
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发表时间：
2023-08-12
影响因子：
4.3
通讯作者：
Song，Jinlin
中科院分区：
文献类型：
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作者：
Li，Lingjie;Jia，Lurong;Song，Jinlin
诱导型一氧化氮合酶（iNOS）与牙周病的炎症和破骨细胞分化有关。本研究旨在比较牙龈和其他牙周组织之间iNOS生成的时间依赖性变化，并探讨其与早期牙周病中C反应蛋白（CRP）的潜在关联。方法分别建立野生型和基因敲除大鼠牙周病模型（0 ~ 14 d）。在牙龈和其他牙周组织中检测CRP、iNOS和自噬水平的变化。用脂多糖和氯喹处理巨噬细胞，探讨自噬在iNOS产生中的作用。使用Western blotting、免疫染色和酶联免疫吸附法分析iNOS、CRP和自噬相关蛋白。采用实时定量聚合酶链反应检测mRNA表达。采用苏木精和伊红染色进行组织学分析。采用组织蛋白酶K免疫染色和上颌骨显微计算机断层扫描比较牙槽骨吸收情况。结果结扎后第2天，牙周组织中sinos和CRP水平迅速升高，结扎后牙龈中sinos和CRP水平下降较其他牙周组织快。CRP缺乏不能阻止iNOS的产生，但能有效加速iNOS的减少，延缓牙槽骨的骨质流失。CRP对iNOS的影响伴随着自噬的改变，而自噬被敲除CRP而减少。结论CRP对iNOS的调节在牙周病早期表现出时空差异，并可能与自噬有关。这些发现可能有助于牙周病的早期发现和有针对性的治疗。
BackgroundInducible nitric oxide synthase (iNOS) is associated with inflammation and osteoclastic differentiation in periodontal disease. This study was conducted to compare the time‐dependent variation in iNOS production between the gingiva and other periodontal tissues and to explore the potential association with C‐reactive protein (CRP) in early periodontal disease.MethodsLigature‐induced periodontal disease models (0–14 days) were established in wild‐type andCRPknockout rats. Changes in CRP, iNOS, and autophagy levels were examined in the gingiva and other periodontal tissues. Macrophages were treated with lipopolysaccharide and chloroquine to explore the role of autophagy in iNOS production. iNOS, CRP, and autophagy‐related proteins were analyzed using Western blotting, immunostaining, and enzyme‐linked immunosorbent assays. mRNA expression was detected by quantitative real‐time polymerase chain reaction. Hematoxylin and eosin staining was used for histological analysis. Cathepsin K immunostaining and microcomputed tomography of the maxillae were performed to compare alveolar bone resorption.ResultsiNOS and CRP levels increased rapidly in periodontal tissues, as observed on Day 2 of ligature, then decreased more rapidly in the gingiva than in other periodontal tissues. CRP deficiency did not prevent iNOS generation, but effectively accelerated iNOS reduction and delayed alveolar bone loss. The CRP effect on iNOS was accompanied by a change in autophagy, which was reduced byCRPknockout.ConclusionsThe regulation of iNOS by CRP shows temporospatial variation in early periodontal disease and is potentially associated with autophagy. These findings may contribute to the early detection and targeted treatment of periodontal disease.