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Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation
Extracellular regulation of signaling by transforming growth factor (TGF)–β family members is emerging as a key aspect of organ formation and tissue remodeling. In this study, we demonstrate that fibrillin-1 and -2, the structural components of extracellular microfibrils, differentially regulate TGF...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101602/ https://www.ncbi.nlm.nih.gov/pubmed/20855508 http://dx.doi.org/10.1083/jcb.201003089 |
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author | Nistala, Harikiran Lee-Arteaga, Sui Smaldone, Silvia Siciliano, Gabriella Carta, Luca Ono, Robert N. Sengle, Gerhard Arteaga-Solis, Emilio Levasseur, Regis Ducy, Patricia Sakai, Lynn Y. Karsenty, Gerard Ramirez, Francesco |
author_facet | Nistala, Harikiran Lee-Arteaga, Sui Smaldone, Silvia Siciliano, Gabriella Carta, Luca Ono, Robert N. Sengle, Gerhard Arteaga-Solis, Emilio Levasseur, Regis Ducy, Patricia Sakai, Lynn Y. Karsenty, Gerard Ramirez, Francesco |
author_sort | Nistala, Harikiran |
collection | PubMed |
description | Extracellular regulation of signaling by transforming growth factor (TGF)–β family members is emerging as a key aspect of organ formation and tissue remodeling. In this study, we demonstrate that fibrillin-1 and -2, the structural components of extracellular microfibrils, differentially regulate TGF-β and bone morphogenetic protein (BMP) bioavailability in bone. Fibrillin-2–null (Fbn2(−/−)) mice display a low bone mass phenotype that is associated with reduced bone formation in vivo and impaired osteoblast maturation in vitro. This Fbn2(−/−) phenotype is accounted for by improper activation of latent TGF-β that selectively blunts expression of osterix, the transcriptional regulator of osteoblast maturation, and collagen I, the structural template for bone mineralization. Cultured osteoblasts from Fbn1(−/−) mice exhibit improper latent TGF-β activation as well, but mature faster because of increased availability of otherwise matrix-bound BMPs. Additional in vitro evidence excludes a direct role of microfibrils in supporting mineral deposition. Together, these findings identify the extracellular microfibrils as critical regulators of bone formation through the modulation of endogenous TGF-β and BMP signaling. |
format | Text |
id | pubmed-3101602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31016022011-06-06 Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation Nistala, Harikiran Lee-Arteaga, Sui Smaldone, Silvia Siciliano, Gabriella Carta, Luca Ono, Robert N. Sengle, Gerhard Arteaga-Solis, Emilio Levasseur, Regis Ducy, Patricia Sakai, Lynn Y. Karsenty, Gerard Ramirez, Francesco J Cell Biol Research Articles Extracellular regulation of signaling by transforming growth factor (TGF)–β family members is emerging as a key aspect of organ formation and tissue remodeling. In this study, we demonstrate that fibrillin-1 and -2, the structural components of extracellular microfibrils, differentially regulate TGF-β and bone morphogenetic protein (BMP) bioavailability in bone. Fibrillin-2–null (Fbn2(−/−)) mice display a low bone mass phenotype that is associated with reduced bone formation in vivo and impaired osteoblast maturation in vitro. This Fbn2(−/−) phenotype is accounted for by improper activation of latent TGF-β that selectively blunts expression of osterix, the transcriptional regulator of osteoblast maturation, and collagen I, the structural template for bone mineralization. Cultured osteoblasts from Fbn1(−/−) mice exhibit improper latent TGF-β activation as well, but mature faster because of increased availability of otherwise matrix-bound BMPs. Additional in vitro evidence excludes a direct role of microfibrils in supporting mineral deposition. Together, these findings identify the extracellular microfibrils as critical regulators of bone formation through the modulation of endogenous TGF-β and BMP signaling. The Rockefeller University Press 2010-09-20 /pmc/articles/PMC3101602/ /pubmed/20855508 http://dx.doi.org/10.1083/jcb.201003089 Text en © 2010 Nistala et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Nistala, Harikiran Lee-Arteaga, Sui Smaldone, Silvia Siciliano, Gabriella Carta, Luca Ono, Robert N. Sengle, Gerhard Arteaga-Solis, Emilio Levasseur, Regis Ducy, Patricia Sakai, Lynn Y. Karsenty, Gerard Ramirez, Francesco Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation |
title | Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation |
title_full | Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation |
title_fullStr | Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation |
title_full_unstemmed | Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation |
title_short | Fibrillin-1 and -2 differentially modulate endogenous TGF-β and BMP bioavailability during bone formation |
title_sort | fibrillin-1 and -2 differentially modulate endogenous tgf-β and bmp bioavailability during bone formation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101602/ https://www.ncbi.nlm.nih.gov/pubmed/20855508 http://dx.doi.org/10.1083/jcb.201003089 |
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