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Article: Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation
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TitleSodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation
 
AuthorsDai, Z
Chung, SK
Miao, D2
Lau, KS
Chan, AWH1
Kung, AWC
 
Keywordsbone formation
myo-inositol
osteogenesis
Smit1
 
Issue Date2011
 
PublisherAmerican Society for Bone and Mineral Research. The Journal's web site is located at http://www.jbmr.org/view/0/index.html
 
CitationJournal Of Bone And Mineral Research, 2011, v. 26 n. 3, p. 582-590 [How to Cite?]
DOI: http://dx.doi.org/10.1002/jbmr.240
 
Abstractmyo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1 -/-) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1 -/- embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1 -/- mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1 -/- mice and strengthened bone structure in SMIT1 +/+ mice. Although MI content was much lower in SMIT1 -/- mesenchymal cells (MSCs), the I(1,4,5)P 3 signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination. © 2011 American Society for Bone and Mineral Research. Copyright © 2011 American Society for Bone and Mineral Research.
 
ISSN0884-0431
2013 Impact Factor: 6.589
 
DOIhttp://dx.doi.org/10.1002/jbmr.240
 
ISI Accession Number IDWOS:000287827600019
Funding AgencyGrant Number
KC Wong Education Foundation
Osteoporosis and Endocrine Research, the University of Hong Kong
Funding Information:

ZD was supported by the KC Wong Education Foundation. This project was supported by the Osteoporosis and Endocrine Research, the University of Hong Kong.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorDai, Z
 
dc.contributor.authorChung, SK
 
dc.contributor.authorMiao, D
 
dc.contributor.authorLau, KS
 
dc.contributor.authorChan, AWH
 
dc.contributor.authorKung, AWC
 
dc.date.accessioned2011-05-11T08:30:38Z
 
dc.date.available2011-05-11T08:30:38Z
 
dc.date.issued2011
 
dc.description.abstractmyo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1 -/-) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1 -/- embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1 -/- mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1 -/- mice and strengthened bone structure in SMIT1 +/+ mice. Although MI content was much lower in SMIT1 -/- mesenchymal cells (MSCs), the I(1,4,5)P 3 signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination. © 2011 American Society for Bone and Mineral Research. Copyright © 2011 American Society for Bone and Mineral Research.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Bone And Mineral Research, 2011, v. 26 n. 3, p. 582-590 [How to Cite?]
DOI: http://dx.doi.org/10.1002/jbmr.240
 
dc.identifier.doihttp://dx.doi.org/10.1002/jbmr.240
 
dc.identifier.epage590
 
dc.identifier.hkuros184858
 
dc.identifier.isiWOS:000287827600019
Funding AgencyGrant Number
KC Wong Education Foundation
Osteoporosis and Endocrine Research, the University of Hong Kong
Funding Information:

ZD was supported by the KC Wong Education Foundation. This project was supported by the Osteoporosis and Endocrine Research, the University of Hong Kong.

 
dc.identifier.issn0884-0431
2013 Impact Factor: 6.589
 
dc.identifier.issue3
 
dc.identifier.openurl
 
dc.identifier.pmid20818642
 
dc.identifier.scopuseid_2-s2.0-79951842355
 
dc.identifier.spage582
 
dc.identifier.urihttp://hdl.handle.net/10722/133316
 
dc.identifier.volume26
 
dc.languageeng
 
dc.publisherAmerican Society for Bone and Mineral Research. The Journal's web site is located at http://www.jbmr.org/view/0/index.html
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Bone and Mineral Research
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAging - metabolism
 
dc.subject.meshAnimals
 
dc.subject.meshBone and Bones - embryology - pathology
 
dc.subject.meshCell Count
 
dc.subject.meshCell Differentiation
 
dc.subject.meshCell Line
 
dc.subject.meshEmbryo, Mammalian - metabolism
 
dc.subject.meshGene Deletion
 
dc.subject.meshInositol - metabolism
 
dc.subject.meshInositol 1,4,5-Trisphosphate - metabolism
 
dc.subject.meshIntracellular Space - metabolism
 
dc.subject.meshMesenchymal Stem Cells - cytology - metabolism
 
dc.subject.meshMice
 
dc.subject.meshOrgan Size
 
dc.subject.meshOsteoblasts - metabolism - pathology
 
dc.subject.meshOsteogenesis
 
dc.subject.meshOsteoporosis - metabolism - pathology
 
dc.subject.meshSymporters - deficiency - metabolism
 
dc.subject.meshTranscription, Genetic
 
dc.subjectbone formation
 
dc.subjectmyo-inositol
 
dc.subjectosteogenesis
 
dc.subjectSmit1
 
dc.titleSodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation
 
dc.typeArticle
 
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<contributor.author>Chan, AWH</contributor.author>
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Author Affiliations
  1. The University of Hong Kong
  2. Nanjing Medical University