Work

Oral microbial extracellular DNA initiates periodontitis through gingival degradation by fibroblast-derived cathepsin K in mice

Year: 2022

Type: article

Abstract: Periodontitis is a highly prevalent disease leading to uncontrolled osteoclastic jawbone resorption and ultimately to edentulism. While the interaction between dysbiotic biofilm communities and host oral barrier immunity has been extensively studied, much less is known about the disease onset mechanism. We report here its initial pathological mechanism revealed by a new in vivo molecular imaging platform using a highly sensitive, Osteoadsorptive Fluogenic Sentinel (OFS) probe that emits a fluorescent signal triggered by cathepsin K (Ctsk) activity. Unexpectedly, a strong OFS signal was already observed before the establishment of chronic inflammation and bone resorption in a ligature-induced mouse model of periodontitis. Single cell RNA sequencing revealed that the cellular source of early Ctsk was not osteoclasts but gingival fibroblasts. Furthermore, the in vivo OFS signal was activated when Toll-Like Receptor 9 (TLR9) ligand or oral biofilm extracellular DNA (eDNA) was topically applied to the mouse palatal gingiva. By contrast, TLR2/4 ligand and planktonic oral microbial mixture failed to activate the in vivo OFS signal. This previously unrecognized interaction between oral microbial eDNA and gingival Ctsk provides a pathological mechanism for disease initiation and a new strategic basis for early diagnosis and intervention of periodontitis.

Source: Communications Biology

DOI: 10.1038/s42003-022-03896-7