Journal
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
Volume 55, Issue 3, Pages 426-437Publisher
SCIENCE PRESS
DOI: 10.3724/abbs.2023018
Keywords
c-di-AMP; periodontal ligament; osteogenesis; adipogenesis
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The study investigates the impact and underlying mechanisms of bacterial second messenger c-di-AMP on the differentiation of human periodontal ligament stem cells (hPDLSCs). The gingival crevicular fluid (GCF) of patients with chronic periodontitis is found to have a higher expression level of c-di-AMP compared to healthy individuals. In vitro experiments show that c-di-AMP affects the differentiation of hPDLSCs by upregulating Toll-like receptors (TLRs). It inhibits osteogenic differentiation through activating NF-kappa B and ERK/MAPK, and promotes adipogenic differentiation through the NF-kappa B and p38/MAPK signaling pathways. Inhibitors of TLRs or activated pathways can reduce the changes induced by c-di-AMP.
Cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger that can be recognized by infected host cells and activate the immunoinflammatory response. The purpose of this study is to demonstrate the effect of c-di-AMP on the differentiation of human periodontal ligament stem cells (hPDLSCs) and its underlying mechanisms. In the present study, we find that the gingival crevicular fluid (GCF) of patients with chronic periodontitis has a higher expression level of c-di-AMP than that of healthy people. In vitro, c-di-AMP influences the differentiation of hPDLSCs by upregulating Toll-like receptors (TLRs); specifically, it inhibits osteogenic differentiation by activating NF-kappa B and ERK/MAPK and promotes adipogenic differentiation through the NF-kappa B and p38/MAPK signaling pathways. Inhibitors of TLRs or activated pathways reduce the changes induced by c-di-AMP. Our results establish the potential correlation among bacterial c-di-AMP, periodontal tissue homeostasis and chronic periodontitis pathogenesis.
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