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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...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
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.
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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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