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Biomechanical stimulation of osteoblast gene expression requires phosphorylation of the RUNX2 transcription factor

dc.contributor.authorLi, Yanen_US
dc.contributor.authorGe, Chunxien_US
dc.contributor.authorLong, Jason Pen_US
dc.contributor.authorBegun, Dana Len_US
dc.contributor.authorRodriguez, Jose Aen_US
dc.contributor.authorGoldstein, Steven Aen_US
dc.contributor.authorFranceschi, Renny Ten_US
dc.date.accessioned2012-06-15T14:33:37Z
dc.date.available2013-08-01T14:04:39Zen_US
dc.date.issued2012-06en_US
dc.identifier.citationLi, Yan; Ge, Chunxi; Long, Jason P; Begun, Dana L; Rodriguez, Jose A; Goldstein, Steven A; Franceschi, Renny T (2012). "Biomechanical stimulation of osteoblast gene expression requires phosphorylation of the RUNX2 transcription factor." Journal of Bone and Mineral Research 27(6): 1263-1274. <http://hdl.handle.net/2027.42/91365>en_US
dc.identifier.issn0884-0431en_US
dc.identifier.issn1523-4681en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/91365
dc.description.abstractBone can adapt its structure in response to mechanical stimuli. At the cellular level, this involves changes in chromatin organization, gene expression, and differentiation, but the underlying mechanisms are poorly understood. Here we report on the involvement of RUNX2, a bone‐related transcription factor, in this process. Fluid flow shear stress loading of preosteoblasts stimulated translocation of extracellular signal‐regulated kinase (ERK)/mitogen‐activated protein kinase (MAPK) to the nucleus where it phosphorylated RUNX2 on the chromatin of target genes, and increased histone acetylation and gene expression. MAPK signaling and two RUNX2 phosphoacceptor sites, S301 and S319, were critical for this response. Similarly, in vivo loading of mouse ulnae dramatically increased ERK and RUNX2 phosphorylation as well as expression of osteoblast‐related genes. These findings establish ERK/MAPK‐mediated phosphorylation of RUNX2 as a critical step in the response of preosteoblasts to dynamic loading and define a novel mechanism to explain how mechanical signals induce gene expression in bone. © 2012 American Society for Bone and Mineral Research.en_US
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherBONEen_US
dc.subject.otherRUNX2en_US
dc.subject.otherMAP KINASEen_US
dc.subject.otherMECHANOTRANSDUCTIONen_US
dc.titleBiomechanical stimulation of osteoblast gene expression requires phosphorylation of the RUNX2 transcription factoren_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelInternal Medicine and Specialitiesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Biological Chemistry, School of Medicine, University of Michigan, Ann Arbor, MI, USAen_US
dc.contributor.affiliationumDept of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave., Ann Arbor, MI 48109‐1078, USA.en_US
dc.contributor.affiliationumOrthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USAen_US
dc.contributor.affiliationumDepartment of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USAen_US
dc.identifier.pmid22337141en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/91365/1/1574_ftp.pdf
dc.identifier.doi10.1002/jbmr.1574en_US
dc.identifier.sourceJournal of Bone and Mineral Researchen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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