Role of the Btk-PLC gamma 2 Signaling Pathway in the Bone Destruction of Apical Periodontitis
Role of the Btk-PLC gamma 2 Signaling Pathway in the Bone Destruction of Apical Periodontitis
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Btk-PLC gamma 2 信号通路在根尖周炎骨破坏中的作用
DOI：
10.1155/2019/8767529
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发表时间：
2019
影响因子：
4.6
通讯作者：
Niu Weidong
中科院分区：
文献类型：
--
作者：
Wang Lina;Zhang Hong;Dong Ming;Zuo Meina;Liu Shuo;Lu Ying;Niu Weidong
慢性根尖周炎以根尖区牙槽骨吸收为特征，是多种炎症介质参与的结果。研究表明，布鲁顿酪氨酸激酶-（Btk-）磷脂酶C γ 2（PLC γ 2）信号通路在骨吸收中起重要作用，但其是否在根尖周炎骨破坏中起作用尚不清楚。因此，本研究通过在体和体外实验验证了Btk和PLC γ 2在根尖周炎骨吸收中的作用。在体实验中，建立小鼠根尖周炎模型，通过破骨细胞计数和HE染色观察根尖骨吸收情况。免疫组化染色检测Btk、PLC γ 2和活化T细胞核因子1（NFATc-1）。在体外实验中，用脂多糖（LPS）刺激破骨细胞前体细胞RAW 264.7，以建立炎症微环境并检测破骨细胞的分化。通过沉默Btk，通过真实的-time qPCR和Western blot检测Btk、PLC γ 2和NFATc-1的表达，并通过酶组织化学染色检测破骨细胞生成，以进一步证实Btk在骨吸收中的作用。研究发现，Btk、PLC γ 2和NFATc-1的表达随着炎症和骨破坏的进展而显著变化，表明Btk和PLC γ 2可能参与根尖周炎炎症和骨吸收的进展。体外实验证实，沉默Btk表达后，破骨细胞的分化以及PLC γ 2和NFATc-1的表达受到显著抑制，但破骨细胞前体细胞可由于促炎因子脂多糖而分化。本研究表明Btk和PLC γ 2是参与根尖炎症反应和骨破坏的关键因素。
Chronic apical periodontitis is characterized by alveolar bone absorption in the apical region and is the result of the participation of various inflammatory mediators. Studies have shown that the Bruton tyrosine kinase‐ (Btk‐) phospholipase Cγ2 (PLCγ2) signaling pathway plays an important role in bone absorption, but it is unknown whether it plays a role in apical periodontitis bone destruction. Therefore, this study verified the role of Btk and PLCγ2 in bone resorption of apical periodontitis byin vivoandin vitroexperiments. In thein vivoexperiment, a mice model of apical periodontitis was established; apical bone resorption was confirmed by the numbers of osteoclasts and HE staining. Btk, PLCγ2, and nuclear factor of activated T‐cells 1 (NFATc‐1) were detected by immunohistochemical staining. In thein vitroexperiment, lipopolysaccharides (LPS) were used to stimulate osteoclast precursor cell RAW264.7 to establish an inflammatory microenvironment and detect osteoclast differentiation. By silencing Btk, the expression of Btk, PLCγ2, and NFATc‐1 was detected by real‐time qPCR and Western blot, and osteoclastogenesis was detected by enzyme histochemical staining to further confirm the role of Btk in bone resorption. It was found that the expression of Btk, PLCγ2, and NFATc‐1 changed significantly with the progression of inflammation and bone destruction, indicating that Btk and PLCγ2 may be involved in the progression of inflammation in apical periodontitis and bone absorption.In vitroexperiments confirmed that the differentiation of osteoclasts and the expression of PLCγ2 and NFATc‐1 were significantly inhibited after silencing Btk expression, but osteoclast precursor cells could be differentiated due to the proinflammatory factor lipopolysaccharide. This study demonstrates that Btk and PLCγ2 are key factors involved in the apical inflammatory response and bone destruction.