Hydrogen Sulfide Maintains Mesenchymal Stem Cell Function and Bone Homeostasis via Regulation of Ca2+ Channel Sulfhydration

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dc.contributor.authorLiu, Yi
dc.contributor.authorYang, Ruili
dc.contributor.authorLiu, Xibao
dc.contributor.authorZhou, Yu
dc.contributor.authorQu, Cunye
dc.contributor.authorKikuiri, Takashi
dc.contributor.authorWang, Songlin
dc.contributor.authorZandi, Ebrahim
dc.contributor.authorDu, Junbao
dc.contributor.authorAmbudkar, Indu S.
dc.contributor.authorShi, Songtao
dc.date2023-05-18T00:26:20.000
dc.date.accessioned2023-05-22T13:13:05Z
dc.date.available2023-05-22T13:13:05Z
dc.date.issued2014-07-03
dc.date.submitted2021-03-04T06:21:31-08:00
dc.description.abstractGaseous 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.
dc.description.commentsAt 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
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/8875
dc.legacy.articleid1270
dc.legacy.fields10.1016/j.stem.2014.03.005
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1270&context=dental_papers&unstamped=1
dc.rights<p>© <2014>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license <a href="http://creativecommons.org/licenses/by-nc-nd/4.0/">http://creativecommons.org/licenses/by-nc-nd/4.0/</a></p>
dc.source.beginpage66
dc.source.endpage78
dc.source.issue166
dc.source.issue1
dc.source.journalDepartmental Papers (Dental)
dc.source.journaltitleCell Stem Cell
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume15
dc.subject.otherDentistry
dc.titleHydrogen Sulfide Maintains Mesenchymal Stem Cell Function and Bone Homeostasis via Regulation of Ca2+ Channel Sulfhydration
dc.typeArticle
digcom.contributor.authorLiu, Yi
digcom.contributor.authorYang, Ruili
digcom.contributor.authorLiu, Xibao
digcom.contributor.authorZhou, Yu
digcom.contributor.authorQu, Cunye
digcom.contributor.authorKikuiri, Takashi
digcom.contributor.authorWang, Songlin
digcom.contributor.authorZandi, Ebrahim
digcom.contributor.authorDu, Junbao
digcom.contributor.authorAmbudkar, Indu S.
digcom.contributor.authorShi, Songtao
digcom.identifierdental_papers/166
digcom.identifier.contextkey21938245
digcom.identifier.submissionpathdental_papers/166
digcom.typearticle
dspace.entity.typePublication
upenn.schoolDepartmentCenterDepartmental Papers (Dental)
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