MicroRNA‐181b‐5p modulates tumor necrosis factor‐α‐induced inflammatory responses by targeting interleukin‐6 in cementoblasts
MicroRNA‐181b‐5p modulates tumor necrosis factor‐α‐induced inflammatory responses by targeting interleukin‐6 in cementoblasts
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DOI：
10.1002/jcp.28837
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发表时间：
2019-12
影响因子：
5.6
通讯作者：
Xiaoxuan Wang;Hualing Sun;Huan Liu;Li Ma;Chenxi Jiang;H. Liao;Shihan Xu;J. Xiang;Z. Cao
中科院分区：
文献类型：
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作者：
Xiaoxuan Wang;Hualing Sun;Huan Liu;Li Ma;Chenxi Jiang;H. Liao;Shihan Xu;J. Xiang;Z. Cao
牙骨质是一种类似骨的矿化组织，是微生物入侵和破坏的屏障。牙骨质也负责牙齿的稳定和保护牙髓免受外界刺激，它是由成牙骨质形成的。虽然它对牙周和根尖周疾病至关重要，但成骨水泥细胞病理生理变化及其炎症反应的机制尚不清楚。MiR - 181b被发现调节血管炎症和内毒素耐受性。在这项研究中，miR - 181b - 5p在肿瘤坏死因子- α (TNF - α)刺激的成水泥细胞中下调，而促炎分子则升高。小鼠根尖周围病变也有类似的结果，这模仿了体内成水泥细胞的炎症环境。生物信息学分析和双荧光素酶报告试验表明miR - 181b - 5p靶向白细胞介素- 6 （IL - 6）。过表达miR - 181b - 5p可负调控IL - 6和促炎趋化因子。Western blot分析和荧光素酶活性报告试验证实miR - 181b - 5p减弱了NF - κB活性。因此，miR - 181b - 5p通过靶向成水泥细胞中的IL - 6和NF - κB信号通路来调节促炎趋化因子的产生。此外，miR - 181b - 5p促进水泥母细胞凋亡，这可能会增强炎症的消退。总的来说，我们的数据显示miR - 181b - 5p是TNF - α -诱导的成水泥细胞炎症反应的负调节因子。
Tooth cementum is a bone‐like mineralized tissue and serves as a microbial barrier against invasion and destruction. Cementum is also responsible for tooth stability and defending pulp from outside stimuli, which is formed by cementoblasts. Although it is crucial for periodontal and periapical diseases, the mechanisms underlying the pathophysiological changes of cementoblasts and their inflammatory responses remain unclear. MiR‐181b is found to modulate vascular inflammation and endotoxin tolerance. In this study, miR‐181b‐5p was downregulated in tumor necrosis factor‐α (TNF‐α)‐stimulated cementoblasts, whereas proinflammatory molecules increased. The mouse periapical lesions have similar results, which imitate an inflammatory environment for cementoblasts in vivo. The bioinformatics analysis and dual luciferase reporter assay suggested that miR‐181b‐5p targeted interleukin‐6 (IL‐6). Overexpressing miR‐181b‐5p negatively regulated IL‐6 and proinflammatory chemokine. Western blot analysis and luciferase activity reporter assay verified that miR‐181b‐5p weakened the NF‐κB activity. Hence, miR‐181b‐5p moderated proinflammatory chemokine production by targeting IL‐6 in cementoblasts and NF‐κB signaling pathway was involved. Furthermore, miR‐181b‐5p promoted cementoblast apoptosis, which may enhance the resolution of inflammation. Overall, our data revealed that miR‐181b‐5p was a negative regulator of TNF‐α‐induced inflammatory responses in cementoblasts.