Skeletal Site-Related Variation in Human Trabecular Bone Transcriptome and Signaling 英文参考文献.docVIP

SkeletalSite-RelatedVariationinHumanTrabecular BoneTranscriptomeandSignaling SatyaS.Varanasi1.,OleK.Olstad2.,DanielC.Swan3,PaulSanderson4,VigdisT.Gautvik2,6 ,Sjur Reppe2,6,RogerM.Francis5,KaareM.Gautvik2,6,7,HarishK.Datta1* 1MusculoskeletalResearchGroup,InstituteofCellularMedicine,MedicalSchool,NewcastleUniversity,NewcastleUponTyne,UnitedKingdom,2DepartmentofClinical Biochemistry,OsloUniversityHospital,Ulleva?l,Norway,3BioinformaticsSupportUnit,InstituteforCellandMolecularBiosciences,MedicalSchool,NewcastleUniversity, NewcastleUponTyne,UnitedKingdom,4DepartmentofOrthopaedicSurgery,NewcastleGeneralHospital,NewcastleUponTyne,UnitedKingdom,5InstituteforAgeing andHealth,NewcastleUniversity,NewcastleUponTyne,UnitedKingdom,6InstituteofBasicMedicalSciences,UniversityofOslo,Oslo,Norway,7DepartmentofClinical Chemistry,LovisenbergDeaconHospital,Oslo,Norway Abstract Background:Theskeletalsite-specificinfluenceofmultiplegenesonbonemorphologyisrecognised,butthequestionas tohowtheseinfluencesmaybeexertedatthemolecularandcellularlevelhasnotbeenexplored. Methodology:Toaddressthisquestion,wehavecomparedglobalgeneexpressionprofilesofhumantrabecularbonefrom twodifferentskeletalsitesthatexperiencevastlydifferentdegreesofmechanicalloading,namelybiopsiesfromiliaccrest andlumbarspinallamina. Principal Findings: In the lumbar spine, compared to the iliac crest, the majority of the differentially expressed genes showedsignificantlyincreasedlevelsofexpression;3406transcriptswereup-whilst838weredown-regulated.Interestingly, allgenetranscriptsthathavebeenrecentlydemonstratedtobemarkersofosteocyte,aswellasosteoblastandosteoclast- relatedgenes,weremarkedlyup-regulatedinthespine.Thetranscriptomedataisconsistentwithosteocytenumbersbeing almostidenticalatthetwoanatomicalsites,butsuggestingarelativelylowosteocytefunctionalactivityintheiliaccrest. Similarly, osteoblast and osteoclast expression data suggested similar numbers of the cells, but presented with higher activityinthespinethaniliaccrest.T