Abstract
Hydrogen sulfide (H2S), an endogenous gasotransmitter, mediated a variety of biological processes through multiple signaling pathways, and aberrant H2S metabolism has been associated with mesenchymal stem cell (MSC) dysfunction. Here we employed the small interfering RNA treatment for cystathionine β-synthase (CBS), cystathionine γ-lyase, the main enzymes to synthesize H2S, and CBS-knockout mice to analyze the effect of H2S on dental pulp homeostasis. We showed that H2S deficiency attenuated dental pulp stem cell (DPSC) osteogenic/dentinogenic differentiation in vitro and in vivo with enhanced cell proliferation. Mechanically, H2S facilitated the transient receptor potential action channel subfamily V member 1-mediated calcium (Ca2+) influx, which subsequently activated the β-catenin pathway. While H2S deficiency decreased Ca2+, resulting in glycogen synthase kinase-3β-mediated β-catenin degradation, which controls proliferation and differentiation of DPSCs. Consistently, H2S-deficient mice displayed disturbed pattern of dental pulp and less dentin formation. In this study, we identified a previously unknown mechanism by which H2S regulates DPSC lineage determination and dental pulp homeostasis.
Highlights
Hydrogen sulfide (H2S) could freely diffuse through cell membranes to elicit various cellular events
dental pulp stem cell (DPSC) produced H2S in the culture supernatant, which was downregulated by CBS small interfering RNA or cystathionine γ-lyase (CSE) siRNA treatment but not MPST siRNA treatment (Fig. 1d), and H2S concentration was upregulated by H2S donor NaHS treatment (Fig. 1d)
ALP-positive and dentin sialophosphoprotein (DSPP)-positive cells were detected in the tissues formed by DPSC transplantation in vivo, while ALP-positive and DSPP-positive cells were decreased after CBS or CSE siRNA treatment (Fig. 2e)
Summary
Hydrogen sulfide (H2S) could freely diffuse through cell membranes to elicit various cellular events. Endogenous H2S is essential to maintain differentiation and proliferation of neural stem cells and human-induced pluripotent stem cells, and to restore the function of endothelial progenitor cell and mesenchymal. The oral cavity is abundant with a plethora of bacteria, some of which are well known to produce H2S. When the dynamic ecological equilibrium in the biofilm is disturbed, bacteria may elicit oral diseases such as caries, gingivitis, and periodontitis[8]. Several studies have indicated the role of H2S in dental stem cells[9]. Dental pulp stem cells (DPSCs), isolated from dental pulp, were reported to be highly proliferative and capable of differentiating into a variety of cells including odontoblasts, osteoblasts, adipocytes, and neural cells
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