Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

7-3-2014

Publication Source

Cell Stem Cell

Volume

15

Issue

1

Start Page

66

Last Page

78

DOI

10.1016/j.stem.2014.03.005

Abstract

Gaseous signaling molecules such as hydrogen sulfide (H2S) are produced endogenously and mediate effects through diverse mechanisms. H2S is one such gasotrasmitter which regulates multiple signaling pathways in mammalian cells, and abnormal H2S metabolism has been linked to defects in bone homeostasis. Here, we demonstrate that bone marrow mesenchymal stem cells (BMMSCs) produce H2S to regulate their self-renewal and osteogenic differentiation, and H2S deficiency results in defects in BMMSC differentiation. H2S deficiency causes aberrant intracellular Ca2+ influx, due to reduced sulfhydration of cysteine residues on multiple Ca2+ TRP channels. This decreased Ca2+ flux downregulates PKC/Erk-mediated Wnt/β-catenin signaling which controls osteogenic differentiation of BMMSCs. Consistently, H2S-deficient mice display an osteoporotic phenotype, which can be rescued by small molecules which release H2S. These results demonstrate H2S regulates BMMSCs, and restoring H2S levels via non-toxic donors may provide treatments for diseases such as osteoporosis which can arise from H2S deficiencies.

Copyright/Permission Statement

© <2014>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Comments

At the time of publication, author Songtao Shi was affiliated with the University of Southern California. Currently, he is a faculty member at the School of Dental Medicine at the University of Pennsylvania

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Date Posted: 01 March 2022

This document has been peer reviewed.