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Article: Pre-B-cell leukemia homeobox 1 (PBX1) shows functional and possible genetic association with bone mineral density variation

TitlePre-B-cell leukemia homeobox 1 (PBX1) shows functional and possible genetic association with bone mineral density variation
Authors
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/
Citation
Human Molecular Genetics, 2009, v. 18 n. 4, p. 679-687 How to Cite?
AbstractBone mineral density (BMD) is one of the major determinants of risk for osteoporotic fracture. Multiple studies reveal that peak bone mass is under strong genetic influence. One of the major susceptibility loci for peak spine BMD has been mapped to chromosome 1q21-q23 in the Caucasian population. We have previously replicated this finding in Southern Chinese pedigrees and detected a maximum multipoint log of odds (LOD) score of 2.36 in this region. To further fine-map this region, 380 single-nucleotide polymorphic (SNP) markers were genotyped in 610 sibpairs from 231 families. Several markers were identified in the association analysis as important candidates underlying BMD variation. Among them, successful replication was demonstrated for SNPs in pre-B-cell leukemia homeobox 1 (PBX1) gene in two other unrelated case-control cohorts. The functional role of PBX1 in bone metabolism was examined in vitro using human bone-derived cells (HBDC) and murine MC3T3-E1 pre-osteoblasts. PBX1 mRNA was constitutively expressed in both HBDC and MC3T3-E1 cells. Immunostaining revealed that PBX1 is localized in the nucleus compartment. Silencing of PBX1 by RNAi in MC3T3-E1 cells decreased the expression of Runx2 and Osterix, the critical transcription factors for osteogenesis, but accelerated cell proliferation and bone nodule formation. Overall, our data suggest a genetic and functional association of PBX1 with BMD. © The Author 2008. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/58251
ISSN
2015 Impact Factor: 5.985
2015 SCImago Journal Rankings: 4.288
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant Council
KC Wong Education Foundation
Bone Health Fund
HKU Foundation
Osteoporosis Research Fund and Matching Grant
University of Hong Kong
Funding Information:

This project is supported by Hong Kong Research Grant Council; KC Wong Education Foundation; The Bone Health Fund, HKU Foundation; Osteoporosis Research Fund and Matching Grant of The University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorCheung, CLen_HK
dc.contributor.authorChan, BYYen_HK
dc.contributor.authorChan, Ven_HK
dc.contributor.authorIkegawa, Sen_HK
dc.contributor.authorKou, Ien_HK
dc.contributor.authorNgai, Hen_HK
dc.contributor.authorSmith, Den_HK
dc.contributor.authorLuk, KDKen_HK
dc.contributor.authorHuang, QYen_HK
dc.contributor.authorMori, Sen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorKung, AWCen_HK
dc.date.accessioned2010-05-31T03:26:48Z-
dc.date.available2010-05-31T03:26:48Z-
dc.date.issued2009en_HK
dc.identifier.citationHuman Molecular Genetics, 2009, v. 18 n. 4, p. 679-687en_HK
dc.identifier.issn0964-6906en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58251-
dc.description.abstractBone mineral density (BMD) is one of the major determinants of risk for osteoporotic fracture. Multiple studies reveal that peak bone mass is under strong genetic influence. One of the major susceptibility loci for peak spine BMD has been mapped to chromosome 1q21-q23 in the Caucasian population. We have previously replicated this finding in Southern Chinese pedigrees and detected a maximum multipoint log of odds (LOD) score of 2.36 in this region. To further fine-map this region, 380 single-nucleotide polymorphic (SNP) markers were genotyped in 610 sibpairs from 231 families. Several markers were identified in the association analysis as important candidates underlying BMD variation. Among them, successful replication was demonstrated for SNPs in pre-B-cell leukemia homeobox 1 (PBX1) gene in two other unrelated case-control cohorts. The functional role of PBX1 in bone metabolism was examined in vitro using human bone-derived cells (HBDC) and murine MC3T3-E1 pre-osteoblasts. PBX1 mRNA was constitutively expressed in both HBDC and MC3T3-E1 cells. Immunostaining revealed that PBX1 is localized in the nucleus compartment. Silencing of PBX1 by RNAi in MC3T3-E1 cells decreased the expression of Runx2 and Osterix, the critical transcription factors for osteogenesis, but accelerated cell proliferation and bone nodule formation. Overall, our data suggest a genetic and functional association of PBX1 with BMD. © The Author 2008. Published by Oxford University Press. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://hmg.oxfordjournals.org/en_HK
dc.relation.ispartofHuman Molecular Geneticsen_HK
dc.rightsHuman Molecular Genetics. Copyright © Oxford University Press.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAsian Continental Ancestry Group - geneticsen_HK
dc.subject.meshBone Densityen_HK
dc.subject.meshCase-Control Studiesen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshChinaen_HK
dc.subject.meshCohort Studiesen_HK
dc.subject.meshDNA-Binding Proteins - genetics - metabolismen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshHumansen_HK
dc.subject.meshJapanen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshOsteoblasts - metabolismen_HK
dc.subject.meshOsteoporosis - genetics - metabolismen_HK
dc.subject.meshPedigreeen_HK
dc.subject.meshPolymorphism, Single Nucleotideen_HK
dc.subject.meshProto-Oncogene Proteins - genetics - metabolismen_HK
dc.titlePre-B-cell leukemia homeobox 1 (PBX1) shows functional and possible genetic association with bone mineral density variationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0964-6906&volume=18&spage=679&epage=687&date=2009&atitle=Pre-B-cell+leukemia+homeobox+1+(PBX1)+shows+functional+and+possible+genetic+association+with+bone+mineral+density+variationen_HK
dc.identifier.emailCheung, CL: lung1212@hku.hken_HK
dc.identifier.emailChan, V: vnychana@hkucc.hku.hken_HK
dc.identifier.emailLuk, KDK: hcm21000@hku.hken_HK
dc.identifier.emailHuang, QY: qyhuang@hotmail.comen_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailKung, AWC: awckung@hku.hken_HK
dc.identifier.authorityCheung, CL=rp01749en_HK
dc.identifier.authorityChan, V=rp00320en_HK
dc.identifier.authorityLuk, KDK=rp00333en_HK
dc.identifier.authorityHuang, QY=rp00521en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityKung, AWC=rp00368en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/hmg/ddn397en_HK
dc.identifier.pmid19064610-
dc.identifier.scopuseid_2-s2.0-58949102957en_HK
dc.identifier.hkuros161215en_HK
dc.identifier.hkuros155802-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58949102957&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue4en_HK
dc.identifier.spage679en_HK
dc.identifier.epage687en_HK
dc.identifier.isiWOS:000262719900008-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridCheung, CL=14520953400en_HK
dc.identifier.scopusauthoridChan, BYY=18333466100en_HK
dc.identifier.scopusauthoridChan, V=7202654865en_HK
dc.identifier.scopusauthoridIkegawa, S=7102780383en_HK
dc.identifier.scopusauthoridKou, I=22985136000en_HK
dc.identifier.scopusauthoridNgai, H=8528923200en_HK
dc.identifier.scopusauthoridSmith, D=7410351143en_HK
dc.identifier.scopusauthoridLuk, KDK=7201921573en_HK
dc.identifier.scopusauthoridHuang, QY=7403630787en_HK
dc.identifier.scopusauthoridMori, S=7403976616en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridKung, AWC=7102322339en_HK

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