Prophylactic supplement with melatonin successfully suppresses the pathogenesis of periodontitis through normalizing RANKL/OPG ratio and depressing the TLR4/MyD88 signaling pathway
Prophylactic supplement with melatonin successfully suppresses the pathogenesis of periodontitis through normalizing RANKL/OPG ratio and depressing the TLR4/MyD88 signaling pathway
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DOI：
10.1111/jpi.12464
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发表时间：
2018-04
影响因子：
10.3
通讯作者：
Ting-Yi Renn;Yung-Kai Huang;Sheng-Wei Feng;Hsiao-Wei Wang;W. Lee;Che-Tong Lin;T. Burnouf;Li-You Che
中科院分区：
文献类型：
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作者：
Ting-Yi Renn;Yung-Kai Huang;Sheng-Wei Feng;Hsiao-Wei Wang;W. Lee;Che-Tong Lin;T. Burnouf;Li-You Che
牙周炎是一种以牙龈炎症和牙槽骨吸收为特征的炎症性疾病。由促炎细胞因子产生增强引起的核因子-κ B配体/骨保护素受体激活剂（RANKL/OPG）信号传导受损在PD发病机制中起重要作用。考虑到褪黑激素具有显著的抗炎特性，本研究旨在确定褪黑激素预防性治疗是否能有效地使RANKL/OPG信号正常化，抑制Toll样受体4/髓样分化因子88（TLR 4/MyD 88）介导的促炎细胞因子激活，并成功抑制PD的发病机制。在成年大鼠中通过将结扎线放置在磨牙龈下区域来诱导PD。在PD诱导前14天，连续28天腹腔注射10、50或100 mg/kg褪黑激素。采用生化法和酶联免疫吸附法分别检测TLR 4/MyD 88活性、RANKL、OPG、白细胞介素1β、白细胞介素6和肿瘤坏死因子α水平。通过扫描电子显微镜、微型计算机断层扫描和能量色散X射线光谱进一步评价骨丢失程度、骨矿物质强度和钙强度。结果表明，PD后检测到较高的RANKL/OPG比值、TLR 4/MyD 88活性和促炎细胞因子水平。生化检查结果受损，伴有严重骨丢失和钙强度降低。然而，在用褪黑激素预处理的大鼠中，所有上述参数成功地恢复到接近正常水平，在接受100 mg/kg的大鼠中观察到最大变化。由于褪黑激素预防性治疗通过抑制TLR 4/MyD 88介导的促炎细胞因子产生有效地使RANKL/OPG信号正常化，因此褪黑激素饮食补充剂可作为加强口腔健康以对抗PD诱导的破坏性损伤的高级策略。
Periodontitis (PD) is an inflammatory disease characterized by gingival inflammation and resorption of alveolar bone. Impaired receptor activator of nuclear factor‐kappa B ligand/osteoprotegerin (RANKL/OPG) signaling caused by enhanced production of pro‐inflammatory cytokines plays an essential role in the pathogenesis of PD. Considering melatonin possesses significant anti‐inflammatory property, this study aimed to determine whether prophylactic treatment with melatonin would effectively normalize RANKL/OPG signaling, depress toll‐like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88)‐mediated pro‐inflammatory cytokine activation, and successfully suppress the pathogenesis of PD. PD was induced in adult rats by placing the ligature at molar subgingival regions. Fourteen days before PD induction, 10, 50, or 100 mg/kg of melatonin was intraperitoneally injected for consecutive 28 days. Biochemical and enzyme‐linked immunosorbent assay were used to detect TLR4/MyD88 activity, RANKL, OPG, interleukin 1β, interleukin 6, and tumor necrosis factor‐α levels, respectively. The extent of bone loss, bone mineral intensity, and calcium intensity was further evaluated by scanning electron microscopy, micro‐computed tomography, and energy‐dispersive X‐ray spectroscopy. Results indicated that high RANKL/OPG ratio, TLR4/MyD88 activity, and pro‐inflammatory cytokine levels were detected following PD. Impaired biochemical findings paralleled well with severe bone loss and reduced calcium intensity. However, in rats pretreated with melatonin, all above parameters were successfully returned to nearly normal levels with maximal change observed in rats receiving 100 mg/kg. As prophylactic treatment with melatonin effectively normalizes RANKL/OPG signaling by depressing TLR4/MyD88‐mediated pro‐inflammatory cytokine production, dietary supplement with melatonin may serve as an advanced strategy to strengthen oral health to counteract PD‐induced destructive damage.