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

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 ?-synthase (CBS), cystathionine ?-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 ?-catenin pathway. While H₂S deficiency decreased Ca²⁺, resulting in glycogen synthase kinase-3?-mediated ?-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.

SUBMITTER: Yang R

PROVIDER: S-EPMC6060166 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Yang Ruili R Liu Yi Y Yu Tingting T Liu Dawei D Shi Songtao S Zhou Yongsheng Y Zhou Yanheng Y

Cell death discovery 20180627

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. ...[more]

PMID: 30062050

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Project description:BackgroundDental pulp stem cells (DPSCs) have been developed as a potential source of mesenchymal stem cells (MSCs) for regeneration of dental pulp and other tissues. However, further strategies to isolate highly functional DPSCs beyond the colony-forming methods are required. We have demonstrated the safety and efficacy of DPSCs isolated by G-CSF-induced mobilization and cultured under normoxia (mobilized DPSCs, MDPSCs) for pulp regeneration. The device for isolation of MDPSCs, however, is not cost-effective and requires a prolonged cell culture period. It is well known that MSCs cultured under hypoxic-preconditions improved MSC proliferation activity and stemness. Therefore, in this investigation, we attempted to improve the clinical utility of DPSCs by hypoxia-preconditioned DPSCs (hpDPSCs) compared with MDPSCs to improve the potential clinical utility for pulp regeneration in endodontic dentistry.MethodsColony-forming DPSCs were isolated and preconditioned with hypoxia in a stable closed cultured system and compared with MDPSCs isolated from the individual dog teeth. We examined the proliferation rate, migration potential, anti-apoptotic activity, and gene expression of the stem cell markers and angiogenic/neurotrophic factors. Trophic effects of the conditioned medium (CM) were also evaluated. In addition, the expression of immunomodulatory molecules upon stimulation with IFN-γ was investigated. The pulp regenerative potential and transplantation safety of hpDPSCs were further assessed in pulpectomized teeth in dogs by histological and immunohistochemical analyses and by chemistry of the blood and urine tests.ResultshpDPSCs demonstrated higher proliferation rate and expression of a major regulator of oxygen homeostasis, HIF-1α, and a stem cell marker, CXCR-4. The direct migratory activity of hpDPSCs in response to G-CSF was significantly higher than MDPSCs. The CM of hpDPSCs stimulated neurite extension. However, there were no changes in angiogenic, migration, and anti-apoptotic activities compared with the CM of MDPSCs. The expression of immunomodulatory gene, PTGE was significantly upregulated by IFN gamma in hpDPSCs compared with MDPSCs. However, no difference in nitric oxide was observed. The regenerated pulp tissue was quantitatively and qualitatively similar in hpDPSC transplants compared with MDPSC transplants in dog teeth. There was no evidence of toxicity or adverse events of the hpDPSC transplantation.ConclusionsThese results demonstrated that the efficacy of hpDPSCs for pulp regeneration was identical, although hpDPSCs improved stem cell properties compared to MDPSCs, suggesting their potential clinical utility for pulp regeneration.

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

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

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