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Article: Strontium promotes osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathway

TitleStrontium promotes osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathway
Authors
KeywordsMitogen-activated protein kinase (MAPK) pathway
Osteogenesis
Ras
Runx2
Strontium
Issue Date2009
PublisherS Karger AG. The Journal's web site is located at http://www.karger.com/CPB
Citation
Cellular Physiology and Biochemistry, 2009, v. 23 n. 1-3, p. 165-174 How to Cite?
AbstractStrontium ralenate is a new anti-osteoporosis agent. The cellular and molecular mechanism underlying the anabolic effect of strontium on bone remains to be elucidated. Osteoblasts, the main bone forming cells are known to be derived from bone marrow mesenchymal stem cells (MSCs). The present study therefore aimed to investigate the possible effects of strontium on MSCs and signaling pathways possibly involved. It was firstly demonstrated that strontium treatment significantly increased osteoblast-related gene expression and alkaline phosphatase (ALP) of osteogenic-differentiating MSCs. Accompanying the enhanced osteogenic differentiation, the increased phosphorylation of mitogen-activated protein kinase (MAPK) ERK1/2 and p38 was detected in strontium-treated MSCs. PD98059 and SB203580, selective inhibitors of ERK1/2 kinase and p38, attenuated the effect of strontium on osteogenesis. Furthermore, it was demonstrated that Rat Sarcoma viral oncogene homolog (RAS), an upstream regulator of ERK1/2 and p38, was activated by strontium treatment and siRNA-mediated Ras knockdown inhibited strontium-stimulated expression of osteogenic markers. Finally, the transcriptional activity and phosphorylation level of Runx2 was significantly increased in response to strontium treatment in MSCs. PD98059 and Ras siRNA inhibited the effect of strontium on Runx2 activation. Taken together, these results indicated that strontium can promote osteogenic differentiation of MSCs through activating the Ras/MAPK signaling pathway and the downstream transcription factor Runx2. Copyright © 2009 S. Karger AG.
Persistent Identifierhttp://hdl.handle.net/10722/125204
ISSN
2015 Impact Factor: 4.652
2015 SCImago Journal Rankings: 1.139
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Innovation and Technology CommissionITS/064/06
HK RGCHKU7147/07E
Funding Information:

This study was supported by Hong Kong Innovation and Technology Commission (ITS/064/06) and HK RGC (HKU7147/07E).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorPeng, Sen_HK
dc.contributor.authorZhou, Gen_HK
dc.contributor.authorLuk, KDKen_HK
dc.contributor.authorCheung, KMCen_HK
dc.contributor.authorLi, Zen_HK
dc.contributor.authorLam, WMen_HK
dc.contributor.authorZhou, Zen_HK
dc.contributor.authorLu, WWen_HK
dc.date.accessioned2010-10-31T11:17:20Z-
dc.date.available2010-10-31T11:17:20Z-
dc.date.issued2009en_HK
dc.identifier.citationCellular Physiology and Biochemistry, 2009, v. 23 n. 1-3, p. 165-174en_HK
dc.identifier.issn1015-8987en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125204-
dc.description.abstractStrontium ralenate is a new anti-osteoporosis agent. The cellular and molecular mechanism underlying the anabolic effect of strontium on bone remains to be elucidated. Osteoblasts, the main bone forming cells are known to be derived from bone marrow mesenchymal stem cells (MSCs). The present study therefore aimed to investigate the possible effects of strontium on MSCs and signaling pathways possibly involved. It was firstly demonstrated that strontium treatment significantly increased osteoblast-related gene expression and alkaline phosphatase (ALP) of osteogenic-differentiating MSCs. Accompanying the enhanced osteogenic differentiation, the increased phosphorylation of mitogen-activated protein kinase (MAPK) ERK1/2 and p38 was detected in strontium-treated MSCs. PD98059 and SB203580, selective inhibitors of ERK1/2 kinase and p38, attenuated the effect of strontium on osteogenesis. Furthermore, it was demonstrated that Rat Sarcoma viral oncogene homolog (RAS), an upstream regulator of ERK1/2 and p38, was activated by strontium treatment and siRNA-mediated Ras knockdown inhibited strontium-stimulated expression of osteogenic markers. Finally, the transcriptional activity and phosphorylation level of Runx2 was significantly increased in response to strontium treatment in MSCs. PD98059 and Ras siRNA inhibited the effect of strontium on Runx2 activation. Taken together, these results indicated that strontium can promote osteogenic differentiation of MSCs through activating the Ras/MAPK signaling pathway and the downstream transcription factor Runx2. Copyright © 2009 S. Karger AG.en_HK
dc.languageengen_HK
dc.publisherS Karger AG. The Journal's web site is located at http://www.karger.com/CPBen_HK
dc.relation.ispartofCellular Physiology and Biochemistryen_HK
dc.subjectMitogen-activated protein kinase (MAPK) pathwayen_HK
dc.subjectOsteogenesisen_HK
dc.subjectRasen_HK
dc.subjectRunx2en_HK
dc.subjectStrontiumen_HK
dc.subject.meshMesenchymal Stem Cells - cytology - drug effects-
dc.subject.meshOsteogenesis - drug effects-
dc.subject.meshSignal Transduction - drug effects-
dc.subject.meshStrontium - pharmacology-
dc.subject.meshras Proteins - genetics - metabolism-
dc.titleStrontium promotes osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1015-8987&volume=23&issue=1-3&spage=165&epage=174&date=2009&atitle=Strontium+Promotes+Osteogenic+Differentiation+of+Mesenchymal+Stem+Cells+Through+the+Ras/MAPK+Signaling+Pathwayen_HK
dc.identifier.emailZhou, G:wormoscz@gmail.comen_HK
dc.identifier.emailLuk, KDK:hcm21000@hku.hken_HK
dc.identifier.emailCheung, KMC:cheungmc@hku.hken_HK
dc.identifier.emailZhou, Z:zhongjun@hkucc.hku.hken_HK
dc.identifier.emailLu, WW:wwlu@hku.hken_HK
dc.identifier.authorityZhou, G=rp00527en_HK
dc.identifier.authorityLuk, KDK=rp00333en_HK
dc.identifier.authorityCheung, KMC=rp00387en_HK
dc.identifier.authorityZhou, Z=rp00503en_HK
dc.identifier.authorityLu, WW=rp00411en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1159/000204105en_HK
dc.identifier.pmid19255511en_HK
dc.identifier.scopuseid_2-s2.0-60549085756en_HK
dc.identifier.hkuros180247en_HK
dc.identifier.hkuros166598-
dc.identifier.hkuros165507-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-60549085756&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume23en_HK
dc.identifier.issue1-3en_HK
dc.identifier.spage165en_HK
dc.identifier.epage174en_HK
dc.identifier.isiWOS:000263534300017-
dc.publisher.placeSwitzerlanden_HK
dc.relation.projectNovel Strontium Hydroxyapatite Nanowhisker (Sr-HA-Nano) reinforced bioactive cement for bone fracture treatment-
dc.identifier.scopusauthoridPeng, S=13402746900en_HK
dc.identifier.scopusauthoridZhou, G=23394245100en_HK
dc.identifier.scopusauthoridLuk, KDK=7201921573en_HK
dc.identifier.scopusauthoridCheung, KMC=7402406754en_HK
dc.identifier.scopusauthoridLi, Z=35784563200en_HK
dc.identifier.scopusauthoridLam, WM=13403256300en_HK
dc.identifier.scopusauthoridZhou, Z=8631856300en_HK
dc.identifier.scopusauthoridLu, WW=7404215221en_HK

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