File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The molecular and cellular basis of exostosis formation in hereditary multiple exostoses

TitleThe molecular and cellular basis of exostosis formation in hereditary multiple exostoses
Authors
Issue Date2008
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/IEP
Citation
International Journal Of Experimental Pathology, 2008, v. 89 n. 5, p. 321-331 How to Cite?
AbstractThe different clinical entities of osteochondromas, hereditary multiple exostoses (HME) and non-familial solitary exostosis, are known to express localized exostoses in their joint metaphyseal cartilage. In the current study biopsies of osteochondromas patients were screened with respect to a number of cellular and molecular parameters. Specifically, cartilaginous biopsy samples of nine HME patients, 10 solitary exostosis patients and 10 articular cartilages of control subjects were collected and cell cultures were established. Results obtained showed that one of the two HME samples that underwent DNA sequencing analysis (HME-1) had a novel mutation for an early stop codon, which led to an aberrant protein, migrating at a lower molecular weight position. The EXT-1 mRNA and protein levels in chondrocyte cultures derived from all nine HME patients were elevated, compared with solitary exostosis patients or control subjects. Furthermore, cell cultures of HME patients had significantly decreased pericellular heparan sulphate (HS) in comparison with cultures of solitary exostosis patients or control subjects. Immunohistochemical staining of tissue sections and Western blotting of cell cultures derived from HME patients revealed higher levels of heparanase compared with solitary exostosis patients and of control subjects. Further investigations are needed to determine whether the low pericellular HS levels in HME patients stem from decreased biosynthesis of HS, increased degradation or a combination of both. In conclusion, it appears that due to a mutated glycosyltransferase, the low content of pericellular HS in HME patients leads to the anatomical deformations with exostoses formation. Hence, elevation of HS content in the pericellular regions should be a potential molecular target for correction. © 2008 The Authors.
Persistent Identifierhttp://hdl.handle.net/10722/68293
ISSN
2015 Impact Factor: 2.125
2015 SCImago Journal Rankings: 0.961
ISI Accession Number ID
Funding AgencyGrant Number
Israel Science Foundation1267/04
Hong Kong Research CouncilN_HKU011/00
Funding Information:

This work was conducted by Meirav Trebicz-Geffen as partial fulfilment of the requirements for a PhD degree at the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. This work was supported partially by grant 1267/04 from the Israel Science Foundation and grant N_HKU011/00 from the Hong Kong Research Council.

References

 

DC FieldValueLanguage
dc.contributor.authorTrebiczGeffen, Men_HK
dc.contributor.authorRobinson, Den_HK
dc.contributor.authorEvron, Zen_HK
dc.contributor.authorGlaser, Ten_HK
dc.contributor.authorFridkin, Men_HK
dc.contributor.authorKollander, Yen_HK
dc.contributor.authorVlodavsky, Ien_HK
dc.contributor.authorIlan, Nen_HK
dc.contributor.authorLaw, KFen_HK
dc.contributor.authorCheah, KSEen_HK
dc.contributor.authorChan, Den_HK
dc.contributor.authorWerner, Hen_HK
dc.contributor.authorNevo, Zen_HK
dc.date.accessioned2010-09-06T06:03:12Z-
dc.date.available2010-09-06T06:03:12Z-
dc.date.issued2008en_HK
dc.identifier.citationInternational Journal Of Experimental Pathology, 2008, v. 89 n. 5, p. 321-331en_HK
dc.identifier.issn0959-9673en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68293-
dc.description.abstractThe different clinical entities of osteochondromas, hereditary multiple exostoses (HME) and non-familial solitary exostosis, are known to express localized exostoses in their joint metaphyseal cartilage. In the current study biopsies of osteochondromas patients were screened with respect to a number of cellular and molecular parameters. Specifically, cartilaginous biopsy samples of nine HME patients, 10 solitary exostosis patients and 10 articular cartilages of control subjects were collected and cell cultures were established. Results obtained showed that one of the two HME samples that underwent DNA sequencing analysis (HME-1) had a novel mutation for an early stop codon, which led to an aberrant protein, migrating at a lower molecular weight position. The EXT-1 mRNA and protein levels in chondrocyte cultures derived from all nine HME patients were elevated, compared with solitary exostosis patients or control subjects. Furthermore, cell cultures of HME patients had significantly decreased pericellular heparan sulphate (HS) in comparison with cultures of solitary exostosis patients or control subjects. Immunohistochemical staining of tissue sections and Western blotting of cell cultures derived from HME patients revealed higher levels of heparanase compared with solitary exostosis patients and of control subjects. Further investigations are needed to determine whether the low pericellular HS levels in HME patients stem from decreased biosynthesis of HS, increased degradation or a combination of both. In conclusion, it appears that due to a mutated glycosyltransferase, the low content of pericellular HS in HME patients leads to the anatomical deformations with exostoses formation. Hence, elevation of HS content in the pericellular regions should be a potential molecular target for correction. © 2008 The Authors.en_HK
dc.languageengen_HK
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/IEPen_HK
dc.relation.ispartofInternational Journal of Experimental Pathologyen_HK
dc.rightsInternational Journal of Experimental Pathology. Copyright © Blackwell Publishing Ltd.en_HK
dc.subject.meshAntibody Specificityen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshCase-Control Studiesen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshChondrocytes - metabolism - pathologyen_HK
dc.subject.meshDNA Mutational Analysisen_HK
dc.subject.meshExostoses - genetics - pathologyen_HK
dc.subject.meshExostoses, Multiple Hereditary - geneticsen_HK
dc.subject.meshGene Expressionen_HK
dc.subject.meshGlucuronidase - analysis - geneticsen_HK
dc.subject.meshGlycosaminoglycans - analysis - geneticsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunoblotting - methodsen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshN-Acetylglucosaminyltransferases - analysis - genetics - immunologyen_HK
dc.subject.meshRNA, Messenger - analysisen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction - methodsen_HK
dc.titleThe molecular and cellular basis of exostosis formation in hereditary multiple exostosesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0959-9673&volume=&spage=Epub &epage=&date=2008&atitle=The+molecular+and+cellular+basis+of+exostosis+formation+in+hereditary+multiple+exostoses.+en_HK
dc.identifier.emailCheah, KSE:hrmbdkc@hku.hken_HK
dc.identifier.emailChan, D:chand@hkucc.hku.hken_HK
dc.identifier.authorityCheah, KSE=rp00342en_HK
dc.identifier.authorityChan, D=rp00540en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1365-2613.2008.00589.xen_HK
dc.identifier.pmid18452536-
dc.identifier.scopuseid_2-s2.0-51349126849en_HK
dc.identifier.hkuros149449en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-51349126849&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume89en_HK
dc.identifier.issue5en_HK
dc.identifier.spage321en_HK
dc.identifier.epage331en_HK
dc.identifier.isiWOS:000259149600003-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridTrebiczGeffen, M=8732258300en_HK
dc.identifier.scopusauthoridRobinson, D=7404643502en_HK
dc.identifier.scopusauthoridEvron, Z=6506242676en_HK
dc.identifier.scopusauthoridGlaser, T=7004968892en_HK
dc.identifier.scopusauthoridFridkin, M=7102193501en_HK
dc.identifier.scopusauthoridKollander, Y=6507778690en_HK
dc.identifier.scopusauthoridVlodavsky, I=7102624687en_HK
dc.identifier.scopusauthoridIlan, N=20134795400en_HK
dc.identifier.scopusauthoridLaw, KF=24776036500en_HK
dc.identifier.scopusauthoridCheah, KSE=35387746200en_HK
dc.identifier.scopusauthoridChan, D=7402216545en_HK
dc.identifier.scopusauthoridWerner, H=7402314588en_HK
dc.identifier.scopusauthoridNevo, Z=7005284557en_HK
dc.identifier.citeulike3203688-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats