Cyclic di-adenosine monophosphate regulates the osteogenic and adipogenic differentiation of hPDLSCs via MAPK and NF-κB signaling

Sirui Chen; Zuping Wu; Yuying He; Li Zhu; Jiahe Wang; Hengyi Lin; Jing Xie; Chenchen Zhou; Shujuan Zou

doi:10.3724/abbs.2023018

Cyclic di-adenosine monophosphate regulates the osteogenic and adipogenic differentiation of hPDLSCs via MAPK and NF-κB signaling

Acta Biochim Biophys Sin (Shanghai). 2023 Feb 25;55(3):426-437. doi: 10.3724/abbs.2023018.

Authors

Sirui Chen¹, Zuping Wu¹, Yuying He¹, Li Zhu¹, Jiahe Wang¹, Hengyi Lin¹, Jing Xie¹, Chenchen Zhou¹, Shujuan Zou^{1

2}

Affiliations

¹ State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 China.
² National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 China.

Abstract

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-κB and ERK/MAPK and promotes adipogenic differentiation through the NF-κB 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.

Keywords: adipogenesis; c-di-AMP; osteogenesis; periodontal ligament.

MeSH terms

Adenosine Monophosphate / metabolism
Cell Differentiation
Cells, Cultured
Chronic Periodontitis* / metabolism
Humans
NF-kappa B* / metabolism
Osteogenesis
Periodontal Ligament / metabolism
Stem Cells / metabolism
Toll-Like Receptors / metabolism

Substances

NF-kappa B
Toll-Like Receptors
Adenosine Monophosphate

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (Nos. 81901040 and 82171001 to C. Z., Nos. 81600840 and 81771047 to J.X. and No. 82071150 to S. Z.).