Oral microbial extracellular DNA initiates periodontitis through gingival degradation by fibroblast-derived cathepsin K in mice.
Oral microbial extracellular DNA initiates periodontitis through gingival degradation by fibroblast-derived cathepsin K in mice.
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DOI：
10.1038/s42003-022-03896-7
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发表时间：
2022-09-14
影响因子：
5.9
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中科院分区：
文献类型：
--
作者：
牙周炎是一种高度流行的疾病，导致破骨细胞性颌骨吸收失控，最终导致无牙本质；然而，其发病机制尚未完全阐明。在这里，我们提出了一个初步的病理机制，基于最近开发的骨吸附荧光哨兵(OFS)探针的结果，该探针发出由组织蛋白酶K(CTSK)活性触发的荧光信号。在结扎诱导的小鼠牙周炎模型中，在慢性炎症和骨吸收建立之前观察到强烈的OFS信号。单细胞RNA测序显示牙龈成纤维细胞是早期CTSK的主要细胞来源。当Toll样受体9(TLR9)配体或口腔生物膜细胞外DNA(EDNA)局部应用于小鼠腭部牙龈时，体内的OFS信号被激活。口腔微生物EDNA与牙周成纤维细胞CTSK之间的这种未知的相互作用为牙周炎的早期诊断和治疗提供了致病的病理机制和战略基础。一种高灵敏度的成像探针显示，口腔微生物细胞外DNA触发牙龈成纤维细胞中CTSK的早期活性，引发小鼠牙周炎。
Periodontitis is a highly prevalent disease leading to uncontrolled osteoclastic jawbone resorption and ultimately edentulism; however, the disease onset mechanism has not been fully elucidated. Here we propose a mechanism for initial pathology based on results obtained using a recently developed Osteoadsorptive Fluogenic Sentinel (OFS) probe that emits a fluorescent signal triggered by cathepsin K (Ctsk) activity. In a ligature-induced mouse model of periodontitis, a strong OFS signal is observed before the establishment of chronic inflammation and bone resorption. Single cell RNA sequencing shows gingival fibroblasts to be the primary cellular source of early Ctsk. The in vivo OFS signal is activated when Toll-Like Receptor 9 (TLR9) ligand or oral biofilm extracellular DNA (eDNA) is topically applied to the mouse palatal gingiva. This previously unrecognized interaction between oral microbial eDNA and Ctsk of gingival fibroblasts provides a pathological mechanism for disease initiation and a strategic basis for early diagnosis and treatment of periodontitis. A highly sensitive imaging probe shows that oral microbial extracellular DNA triggers early activity of Ctsk in gingival fibroblasts, initiating periodontitis in mice.
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