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新型蛋白复合物 FAPα/ITGA5 参与根尖周炎的骨破坏。

The novel protein complex FAPα/ITGA5 is involved in the bone destruction of apical periodontitis.

机构信息

Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian, Liaoning 116044, China.

Zhong Shan College of Dalian Medical University, No. 28, Aixian Street, Dalian, Liaoning 116085, China.

出版信息

Int J Biol Macromol. 2024 Feb;259(Pt 1):128200. doi: 10.1016/j.ijbiomac.2023.128200. Epub 2023 Nov 17.

Abstract

The bacteria that invade the periapical tissue of teeth can directly damage tissue cells such as periapical fibroblasts, leading to an inflammatory response in the periapical tissue and ultimately resulting in bone destruction. We investigated the role of fibroblast activation protein α (FAPα) and integrin α5 (ITGA5) in periapical bone destruction. This study found that FAPα and ITGA5 were highly expressed in human tissues from patients with chronic apical periodontitis. Osteoclast differentiation decreased when FAPα or ITGA5 was silenced and inhibited. The results of protein molecular docking showed that FAPα had good binding affinity to ITGA5, and its free energy was -14.5 kcal/mol. Immunofluorescence staining and co-immunoprecipitation showed that FAPα and ITGA5 formed protein complexes in the inflammatory microenvironment. In conclusion, this study proved that FAPα and ITGA5 participate in the regulation of osteoclast differentiation by forming protein complexes in the inflammatory microenvironment, which then regulates the occurrence and development of chronic apical periodontitis.

摘要

侵入牙齿根尖组织的细菌可直接损伤根尖成纤维细胞等组织细胞,引起根尖组织的炎症反应,最终导致骨破坏。我们研究了成纤维细胞激活蛋白α(FAPα)和整合素α5(ITGA5)在根尖骨破坏中的作用。本研究发现,FAPα和 ITGA5 在慢性根尖周炎患者的人组织中高表达。沉默 FAPα 或 ITGA5 可抑制破骨细胞分化。蛋白分子对接结果表明,FAPα 与 ITGA5 具有良好的结合亲和力,其自由能为-14.5kcal/mol。免疫荧光染色和共免疫沉淀显示,FAPα 和 ITGA5 在炎症微环境中形成蛋白复合物。总之,本研究证明 FAPα 和 ITGA5 通过在炎症微环境中形成蛋白复合物参与破骨细胞分化的调节,进而调节慢性根尖周炎的发生和发展。

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