Positive Correlation between Activated CypA/CD147 Signaling and MMP-9 Expression in Mice Inflammatory Periapical Lesion
Positive Correlation between Activated CypA/CD147 Signaling and MMP-9 Expression in Mice Inflammatory Periapical Lesion
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小鼠根尖周炎症病变中激活的 CypA/CD147 信号传导与 MMP-9 表达呈正相关
DOI：
10.1155/2019/8528719
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发表时间：
2019
影响因子：
--
通讯作者：
Peng Bin
中科院分区：
文献类型：
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作者：
Wang Yan qing;Zhang Jie;Zhu Ling xin;Yu Jing jing;Liu Ming wen;Zhu Shen ting;Liu Guo jing;Peng Bin
瞄准亲环素A（CypA）/CD 147信号传导在炎症和骨代谢的调节中起关键作用。本研究旨在探讨CypA/CD 147在小鼠根尖周病变进展中的作用及其与骨吸收的关系。通过暴露40只C57 BL/6 J小鼠的第一下磨牙的牙髓来诱导根尖周病变。在第0、7、14、21、28、35、42和49天处死小鼠。采集下颌骨进行X线成像、显微计算机断层扫描、组织学观察、免疫组织化学、酶组织化学和双重免疫荧光分析。Western blot进一步检测CypA介导的LPS刺激RAW 264. 7细胞后相关分子信号通路的变化。根尖周病变的体积和面积从第0天到第35天增加，并保持稳定，直到第49天。免疫组织化学显示CypA表达水平也从0天到35天增加，直到49天下降，类似于CD 147表达（R2= 0.4423，P < 0.05），破骨细胞数破骨细胞生成相关的基质金属蛋白酶9（MMP-9）的表达（R2= 0.4715，P < 0.05）。连续切片进一步证实CypA和CD 147在破骨细胞上的共定位与免疫组化。免疫荧光分析显示，CypA阳性或CD 147阳性细胞的分布与MMP-9阳性细胞的动态变化呈正相关。经CypA抑制剂处理后，RAW 264. 7细胞中CD 147和MMP-9的表达均明显下调（P <0. 05）。本研究揭示了CypA/CD 147信号传导和破骨细胞相关MMP-9表达在小鼠炎性根尖周病变进展中的正相关性。因此，干预CypA/CD 147信号可能为减轻炎症性骨吸收提供潜在的治疗靶点。
Aim. Cyclophilin A (CypA)/CD147 signaling plays critical roles in the regulation of inflammation and bone metabolism. This study aimed to investigate the participation of CypA/CD147 in mice periapical lesions progression and its relationship with bone resorption.Methodology. Periapical lesions were induced by pulp exposure in the first lower molars of 40 C57BL/6J mice. The mice were sacrificed on days 0, 7, 14, 21, 28, 35, 42, and 49. Mandibles were harvested for X‐ray imaging, microcomputed tomography scanning, histologic observation, immunohistochemistry, enzyme histochemistry, and double immunofluorescence analysis. Western blot was employed to further detect the related molecular signaling pathways in LPS‐stimulated RAW 264.7 cells treated with CypA inhibitor.Results. The volume and area of the periapical lesions increased from day 0 to day 35 and remained comparably stable until day 49. Immunohistochemistry demonstrated that the CypA expression levels also increased from day 0 to day 35 and decreased until day 49, similar to CD147 expression (R2= 0.4423, P < 0.05), osteoclast number (R2= 0.5101, P < 0.01), and the expression of osteoclastogenesis‐related matrix metalloproteinase 9 (MMP‐9) (R2= 0.4715, P < 0.05). Serial sections further confirmed the colocalization of CypA and CD147 on osteoclasts with immunohistochemistry. And the distribution of CypA‐positive or CD147‐positive cells was positively correlated with the dynamics of MMP‐9‐positive cells by using immunofluorescence analysis. Furthermore, CD147 and MMP‐9 expression in RAW 264.7 cells were both downregulated with CypA inhibitor treatment (P < 0.05).Conclusions. The present study reveals the positive correlation of CypA/CD147 signaling and osteoclast‐related MMP‐9 expression in mice inflammatory periapical lesions progression. Therefore, intervention of CypA/CD147 signaling could probably provide a potential therapeutic target for attenuating inflammatory bone resorption.