Yang Ruili, Liu Yi, Yu Tingting, Liu Dawei, Shi Songtao, Zhou Yongsheng, Zhou Yanheng
1Department of Orthodontics, Peking University School and Hospital of Stomatology, 100081 Beijing, China.
National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 100081 Beijing, China.
Cell Death Discov. 2018 Jun 27;4:1. doi: 10.1038/s41420-018-0071-4. eCollection 2018.
Hydrogen sulfide (HS), an endogenous gasotransmitter, mediated a variety of biological processes through multiple signaling pathways, and aberrant HS 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 HS, and CBS-knockout mice to analyze the effect of HS on dental pulp homeostasis. We showed that HS deficiency attenuated dental pulp stem cell (DPSC) osteogenic/dentinogenic differentiation in vitro and in vivo with enhanced cell proliferation. Mechanically, HS facilitated the transient receptor potential action channel subfamily V member 1-mediated calcium (Ca influx, which subsequently activated the β-catenin pathway. While HS deficiency decreased Ca, resulting in glycogen synthase kinase-3β-mediated β-catenin degradation, which controls proliferation and differentiation of DPSCs. Consistently, HS-deficient mice displayed disturbed pattern of dental pulp and less dentin formation. In this study, we identified a previously unknown mechanism by which HS regulates DPSC lineage determination and dental pulp homeostasis.
硫化氢（HS）作为一种内源性气体信号分子，通过多种信号通路介导多种生物学过程，而HS代谢异常与间充质干细胞（MSC）功能障碍有关。在此，我们采用小干扰RNA处理胱硫醚β-合酶（CBS）、胱硫醚γ-裂解酶（合成HS的主要酶），并利用CBS基因敲除小鼠来分析HS对牙髓稳态的影响。我们发现，HS缺乏在体外和体内均减弱了牙髓干细胞（DPSC）的成骨/成牙本质分化，同时增强了细胞增殖。机制上，HS促进瞬时受体电位香草酸受体1介导的钙（Ca）内流，随后激活β-连环蛋白通路。而HS缺乏则减少Ca内流，导致糖原合酶激酶-3β介导的β-连环蛋白降解，从而控制DPSC的增殖和分化。同样，HS缺乏的小鼠牙髓模式紊乱，牙本质形成减少。在本研究中，我们确定了一种此前未知的机制，即HS通过该机制调节DPSC谱系决定和牙髓稳态。
