Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2

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dc.citation.issue23
dc.citation.volume143
dc.contributor.authorSalazar, Valerie S.
dc.contributor.authorOhte, Satoshi
dc.contributor.authorCapelo, Luciane Portas [UNIFESP]
dc.contributor.authorGamer, Laura
dc.contributor.authorRosen, Vicki
dc.coverageCambridge
dc.date.accessioned2020-07-31T12:47:05Z
dc.date.available2020-07-31T12:47:05Z
dc.date.issued2016
dc.description.abstractEnhanced BMP or canonical Wnt (cWnt) signaling are therapeutic strategies employed to enhance bone formation and fracture repair, but the mechanisms each pathway utilizes to specify cell fate of bone-forming osteoblasts remain poorly understood. Among all BMPs expressed in bone, we find that singular deficiency of Bmp2 blocks the ability of cWnt signaling to specify osteoblasts from limb bud or bone marrow progenitors. When exposed to cWnts, Bmp2-deficient cells fail to progress through the Runx2/Osx1 checkpoint and thus do not upregulate multiple genes controlling mineral metabolism in osteoblasts. Cells lacking Bmp2 after induction of Osx1 differentiate normally in response to cWnts, suggesting that pre-Osx1(+) osteoprogenitors are an essential source and a target of BMP2. Our analysis furthermore reveals Grainyhead-like 3 (Grhl3) as a transcription factor in the osteoblast gene regulatory network induced during bone development and bone repair, which acts upstream of Osx1 in a BMP2-dependent manner. The Runx2/Osx1 transition therefore receives crucial regulatory inputs from BMP2 that are not compensated for by cWnt signaling, and this is mediated at least in part by induction and activation of Grhl3.en
dc.description.affiliationHarvard Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA
dc.description.affiliationSaitama Med Univ, Res Ctr Genom Med, Div Pathophysiol, 1397-1 Yamane, Hidaka, Saitama 3501241, Japan
dc.description.affiliationUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Rua Talim 330, BR-12231280 Sao Jose Dos Campos, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Rua Talim, 330, São José dos Campos, São Paulo, CEP 12231-280, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS)
dc.description.sponsorshipIDNIH-NIAMS: R01 AR055904
dc.format.extent4352-4367
dc.identifierhttp://dx.doi.org/10.1242/dev.136879
dc.identifier.citationDevelopment. Cambridge, v. 143, n. 23, p. 4352-4367, 2016.
dc.identifier.doi10.1242/dev.136879
dc.identifier.fileWOS000393454100007.pdf
dc.identifier.issn0950-1991
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56580
dc.identifier.wosWOS:000393454100007
dc.language.isoeng
dc.publisherCompany Of Biologists Ltd
dc.relation.ispartofDevelopment
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectBMPen
dc.subjectWnten
dc.subjectOsteoblasten
dc.subjectOsx1en
dc.subjectSp7en
dc.subjectDlx5en
dc.subjectGrhl3en
dc.subjectMouse MLB13 cellsen
dc.titleSpecification of osteoblast cell fate by canonical Wnt signaling requires Bmp2en
dc.typeinfo:eu-repo/semantics/article
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