Treponema denticola-Induced RASA4 Upregulation Mediates Cytoskeletal Dysfunction and MMP-2 Activity in Periodontal Fibroblasts.

Treponema denticola-Induced RASA4 Upregulation Mediates Cytoskeletal Dysfunction and MMP-2 Activity in Periodontal Fibroblasts.
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DOI:
10.3389/fcimb.2021.671968
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发表时间:
2021
影响因子:
5.7
通讯作者:
Kapila YL
Kapila YL
中科院分区:
医学2区
文献类型:
--
作者:
Malone ET;Ganther S;Mena N;Radaic A;Shariati K;Kindberg A;Tafolla C;Kamarajan P;Fenno JC;Zhan L;Kapila YL

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牙周复合体由牙周膜(PDL)、牙槽骨和牙骨质组成,它们共同工作以将机械负荷转化为负责维持稳态环境的生物反应。然而,口腔微生物,在生态失调的条件下,可能会挑战牙周病的背景下的PDL的肌动蛋白动力学特性。为了研究这一过程,我们通过分子和功能细胞测定研究了牙周组织中宿主-微生物的相互作用,并表明人类PDL细胞与齿垢密螺旋体的相互作用通过一种新的肌动蛋白重组信号机制诱导肌动蛋白解聚。这种肌动蛋白重组机制和细胞粘附的丧失是一种病理反应,其特征在于RASA 4 mRNA表达的初始上调,导致基质金属蛋白酶-2活性的增加。该机制对齿垢密螺旋体效应蛋白牙本质素是特异性的,从而揭示了齿垢密螺旋体介导的RASA 4转录激活和肌动蛋白解聚在原代人PDL细胞中的新作用。
The periodontal complex consists of the periodontal ligament (PDL), alveolar bone, and cementum, which work together to turn mechanical load into biological responses that are responsible for maintaining a homeostatic environment. However oral microbes, under conditions of dysbiosis, may challenge the actin dynamic properties of the PDL in the context of periodontal disease. To study this process, we examined host-microbial interactions in the context of the periodontium via molecular and functional cell assays and showed that human PDL cell interactions with Treponema denticola induce actin depolymerization through a novel actin reorganization signaling mechanism. This actin reorganization mechanism and loss of cell adhesion is a pathological response characterized by an initial upregulation of RASA4 mRNA expression resulting in an increase in matrix metalloproteinase-2 activity. This mechanism is specific to the T. denticola effector protein, dentilisin, thereby uncovering a novel effect for Treponema denticola-mediated RASA4 transcriptional activation and actin depolymerization in primary human PDL cells.
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