Hydrogen sulfide maintains dental pulp stem cell function via TRPV1-mediated calcium influx

Hydrogen sulfide (H(2)S), an endogenous gasotransmitter, mediated a variety of biological processes through multiple signaling pathways, and aberrant H(2)S 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 H(2)S, and CBS-knockout mice to analyze the effect of H(2)S on dental pulp homeostasis. We showed that H(2)S deficiency attenuated dental pulp stem cell (DPSC) osteogenic/dentinogenic differentiation in vitro and in vivo with enhanced cell proliferation. Mechanically, H(2)S facilitated the transient receptor potential action channel subfamily V member 1-mediated calcium (Ca(2+)) influx, which subsequently activated the β-catenin pathway. While H(2)S deficiency decreased Ca(2+), resulting in glycogen synthase kinase-3β-mediated β-catenin degradation, which controls proliferation and differentiation of DPSCs. Consistently, H(2)S-deficient mice displayed disturbed pattern of dental pulp and less dentin formation. In this study, we identified a previously unknown mechanism by which H(2)S regulates DPSC lineage determination and dental pulp homeostasis.