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JAK2-STAT3 信号通路参与粪肠球菌诱导的大鼠根尖周病变。

JAK2-STAT3 signaling pathway is involved in rat periapical lesions induced by Enterococcus faecalis.

机构信息

Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, Dalian, China.

Department of Oral Basic science, College of Stomatology, Dalian Medical University, Dalian, China.

出版信息

Oral Dis. 2019 Oct;25(7):1769-1779. doi: 10.1111/odi.13169. Epub 2019 Aug 19.

DOI:10.1111/odi.13169
PMID:31365165
Abstract

OBJECTIVES

This study aimed to investigate the role of JAK2-STAT3 (Janus kinase 2/signal transducer and activator of transcription 3) in periapical disease caused by Enterococcus faecalis, as well as the correlation between lipoteichoic acid (LTA) in E. faecalis and the activity of the JAK2-STAT3 signaling pathway and osteoclast formation.

MATERIALS AND METHODS

A rat model of periapical periodontitis induced by E. faecalis was established. Periapical bone resorption was confirmed by HE staining. The expression of JAK2, p-JAK2, STAT3, and p-STAT3 was assessed with immunohistochemical staining. Osteoclasts were observed through enzyme histochemical staining. LTA acted on mouse osteoclast precursor cells (RAW264.7 cells); a JAK2 inhibitor (AG490) was used to inhibit the JAK2-STAT3 pathway in RAW264.7 cells. The expression of proteins in the JAK2-STAT3 pathway and TRAP (tartrate resistant acid phosphatase) in RAW264.7 cells was also detected.

RESULTS

Rat periapical periodontitis was successfully established and bone resorption peaked at day 21. The expression of critical components in the JAK2-STAT3 pathway increased with the progression of inflammation. LTA promoted the differentiation of RAW264.7 cells into osteoclasts. NFATc1 was highly expressed and was inhibited by AG490.

CONCLUSIONS

JAK2-STAT3 signaling pathway plays an important role in the process of periapical bone resorption and osteoclastogenesis.

摘要

目的

本研究旨在探讨 JAK2-STAT3(Janus 激酶 2/信号转导和转录激活因子 3)在粪肠球菌引起的根尖周病中的作用,以及粪肠球菌中的脂磷壁酸(LTA)与 JAK2-STAT3 信号通路活性和破骨细胞形成的相关性。

材料和方法

建立了由粪肠球菌引起的大鼠根尖周牙周炎模型。通过 HE 染色证实根尖骨吸收。采用免疫组织化学染色评估 JAK2、p-JAK2、STAT3 和 p-STAT3 的表达。通过酶组织化学染色观察破骨细胞。LTA 作用于小鼠破骨细胞前体细胞(RAW264.7 细胞);使用 JAK2 抑制剂(AG490)抑制 RAW264.7 细胞中的 JAK2-STAT3 通路。还检测了 RAW264.7 细胞中 JAK2-STAT3 通路和 TRAP(抗酒石酸酸性磷酸酶)的蛋白表达。

结果

成功建立了大鼠根尖周牙周炎模型,骨吸收在第 21 天达到高峰。JAK2-STAT3 通路的关键组成部分的表达随着炎症的进展而增加。LTA 促进 RAW264.7 细胞向破骨细胞分化。NFATc1 高表达,被 AG490 抑制。

结论

JAK2-STAT3 信号通路在根尖周骨吸收和破骨细胞形成过程中发挥重要作用。

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