Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/56580 http://dx.doi.org/10.1242/dev.136879 |
Resumo: | Enhanced 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. |
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Salazar, Valerie S.Ohte, SatoshiCapelo, Luciane Portas [UNIFESP]Gamer, LauraRosen, Vicki2020-07-31T12:47:05Z2020-07-31T12:47:05Z2016Development. Cambridge, v. 143, n. 23, p. 4352-4367, 2016.0950-1991https://repositorio.unifesp.br/handle/11600/56580http://dx.doi.org/10.1242/dev.136879WOS000393454100007.pdf10.1242/dev.136879WOS:000393454100007Enhanced 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.National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH-NIAMS)Harvard Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USASaitama Med Univ, Res Ctr Genom Med, Div Pathophysiol, 1397-1 Yamane, Hidaka, Saitama 3501241, JapanUniv Fed Sao Paulo, Inst Ciencia & Tecnol, Rua Talim 330, BR-12231280 Sao Jose Dos Campos, SP, BrazilUniversidade Federal de São Paulo, Rua Talim, 330, São José dos Campos, São Paulo, CEP 12231-280, BrazilNIH-NIAMS: R01 AR055904Web of Science4352-4367engCompany Of Biologists LtdDevelopmentBMPWntOsteoblastOsx1Sp7Dlx5Grhl3Mouse MLB13 cellsSpecification of osteoblast cell fate by canonical Wnt signaling requires Bmp2info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCambridge14323info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000393454100007.pdfapplication/pdf2316303${dspace.ui.url}/bitstream/11600/56580/1/WOS000393454100007.pdf333dbf9a6a9d482446d90ed02f3ab78cMD51open accessTEXTWOS000393454100007.pdf.txtWOS000393454100007.pdf.txtExtracted texttext/plain77773${dspace.ui.url}/bitstream/11600/56580/8/WOS000393454100007.pdf.txt66d882c23b828c14591a12c01622e487MD58open accessTHUMBNAILWOS000393454100007.pdf.jpgWOS000393454100007.pdf.jpgIM Thumbnailimage/jpeg9013${dspace.ui.url}/bitstream/11600/56580/10/WOS000393454100007.pdf.jpg7932a34370352388e853995c43f96299MD510open access11600/565802023-06-05 19:08:47.009open accessoai:repositorio.unifesp.br:11600/56580Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:08:47Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2 |
title |
Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2 |
spellingShingle |
Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2 Salazar, Valerie S. BMP Wnt Osteoblast Osx1 Sp7 Dlx5 Grhl3 Mouse MLB13 cells |
title_short |
Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2 |
title_full |
Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2 |
title_fullStr |
Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2 |
title_full_unstemmed |
Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2 |
title_sort |
Specification of osteoblast cell fate by canonical Wnt signaling requires Bmp2 |
author |
Salazar, Valerie S. |
author_facet |
Salazar, Valerie S. Ohte, Satoshi Capelo, Luciane Portas [UNIFESP] Gamer, Laura Rosen, Vicki |
author_role |
author |
author2 |
Ohte, Satoshi Capelo, Luciane Portas [UNIFESP] Gamer, Laura Rosen, Vicki |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Salazar, Valerie S. Ohte, Satoshi Capelo, Luciane Portas [UNIFESP] Gamer, Laura Rosen, Vicki |
dc.subject.eng.fl_str_mv |
BMP Wnt Osteoblast Osx1 Sp7 Dlx5 Grhl3 Mouse MLB13 cells |
topic |
BMP Wnt Osteoblast Osx1 Sp7 Dlx5 Grhl3 Mouse MLB13 cells |
description |
Enhanced 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. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016 |
dc.date.accessioned.fl_str_mv |
2020-07-31T12:47:05Z |
dc.date.available.fl_str_mv |
2020-07-31T12:47:05Z |
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info:eu-repo/semantics/publishedVersion |
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dc.identifier.citation.fl_str_mv |
Development. Cambridge, v. 143, n. 23, p. 4352-4367, 2016. |
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https://repositorio.unifesp.br/handle/11600/56580 http://dx.doi.org/10.1242/dev.136879 |
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0950-1991 |
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WOS000393454100007.pdf |
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10.1242/dev.136879 |
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WOS:000393454100007 |
identifier_str_mv |
Development. Cambridge, v. 143, n. 23, p. 4352-4367, 2016. 0950-1991 WOS000393454100007.pdf 10.1242/dev.136879 WOS:000393454100007 |
url |
https://repositorio.unifesp.br/handle/11600/56580 http://dx.doi.org/10.1242/dev.136879 |
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Company Of Biologists Ltd |
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Company Of Biologists Ltd |
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