Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation

c-src deletion in mice leads to osteopetrosis as a result of reduced bone resorption due to an alteration of the osteoclast. We report that deletion/reduction of Src expression enhances osteoblast differentiation and bone formation, contributing to the increase in bone mass. Bone histomorphometry s...

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Main Authors:	Marzia, Marilena, Sims, Natalie A., Voit, Susanne, Migliaccio, Silvia, Taranta, Anna, Bernardini, Silvia, Faraggiana, Tullio, Yoneda, Toshiyuki, Mundy, Gregory R., Boyce, Brendan F., Baron, Roland, Teti, Anna
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2000
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192638/

id	pubmed-2192638
recordtype	oai_dc
spelling	pubmed-21926382008-05-01 Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation Marzia, Marilena Sims, Natalie A. Voit, Susanne Migliaccio, Silvia Taranta, Anna Bernardini, Silvia Faraggiana, Tullio Yoneda, Toshiyuki Mundy, Gregory R. Boyce, Brendan F. Baron, Roland Teti, Anna Original Article c-src deletion in mice leads to osteopetrosis as a result of reduced bone resorption due to an alteration of the osteoclast. We report that deletion/reduction of Src expression enhances osteoblast differentiation and bone formation, contributing to the increase in bone mass. Bone histomorphometry showed that bone formation was increased in Src null compared with wild-type mice. In vitro, alkaline phosphatase (ALP) activity and nodule mineralization were increased in primary calvarial cells and in SV40-immortalized osteoblasts from Src−/− relative to Src+/+ mice. Src-antisense oligodeoxynucleotides (AS-src) reduced Src levels by ∼60% and caused a similar increase in ALP activity and nodule mineralization in primary osteoblasts in vitro. Reduction in cell proliferation was observed in primary and immortalized Src−/− osteoblasts and in normal osteoblasts incubated with the AS-src. Semiquantitative reverse transcriptase-PCR revealed upregulation of ALP, Osf2/Cbfa1 transcription factor, PTH/PTHrP receptor, osteocalcin, and pro-alpha 2(I) collagen in Src-deficient osteoblasts. The expression of the bone matrix protein osteopontin remained unchanged. Based on these results, we conclude that the reduction of Src expression not only inhibits bone resorption, but also stimulates osteoblast differentiation and bone formation, suggesting that the osteogenic cells may contribute to the development of the osteopetrotic phenotype in Src-deficient mice. The Rockefeller University Press 2000-10-16 /pmc/articles/PMC2192638/ /pubmed/11038178 Text en © 2000 The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Marzia, Marilena Sims, Natalie A. Voit, Susanne Migliaccio, Silvia Taranta, Anna Bernardini, Silvia Faraggiana, Tullio Yoneda, Toshiyuki Mundy, Gregory R. Boyce, Brendan F. Baron, Roland Teti, Anna
spellingShingle	Marzia, Marilena Sims, Natalie A. Voit, Susanne Migliaccio, Silvia Taranta, Anna Bernardini, Silvia Faraggiana, Tullio Yoneda, Toshiyuki Mundy, Gregory R. Boyce, Brendan F. Baron, Roland Teti, Anna Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation
author_facet	Marzia, Marilena Sims, Natalie A. Voit, Susanne Migliaccio, Silvia Taranta, Anna Bernardini, Silvia Faraggiana, Tullio Yoneda, Toshiyuki Mundy, Gregory R. Boyce, Brendan F. Baron, Roland Teti, Anna
author_sort	Marzia, Marilena
title	Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation
title_short	Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation
title_full	Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation
title_fullStr	Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation
title_full_unstemmed	Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation
title_sort	decreased c-src expression enhances osteoblast differentiation and bone formation
description	c-src deletion in mice leads to osteopetrosis as a result of reduced bone resorption due to an alteration of the osteoclast. We report that deletion/reduction of Src expression enhances osteoblast differentiation and bone formation, contributing to the increase in bone mass. Bone histomorphometry showed that bone formation was increased in Src null compared with wild-type mice. In vitro, alkaline phosphatase (ALP) activity and nodule mineralization were increased in primary calvarial cells and in SV40-immortalized osteoblasts from Src−/− relative to Src+/+ mice. Src-antisense oligodeoxynucleotides (AS-src) reduced Src levels by ∼60% and caused a similar increase in ALP activity and nodule mineralization in primary osteoblasts in vitro. Reduction in cell proliferation was observed in primary and immortalized Src−/− osteoblasts and in normal osteoblasts incubated with the AS-src. Semiquantitative reverse transcriptase-PCR revealed upregulation of ALP, Osf2/Cbfa1 transcription factor, PTH/PTHrP receptor, osteocalcin, and pro-alpha 2(I) collagen in Src-deficient osteoblasts. The expression of the bone matrix protein osteopontin remained unchanged. Based on these results, we conclude that the reduction of Src expression not only inhibits bone resorption, but also stimulates osteoblast differentiation and bone formation, suggesting that the osteogenic cells may contribute to the development of the osteopetrotic phenotype in Src-deficient mice.
publisher	The Rockefeller University Press
publishDate	2000
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2192638/
_version_	1611430610819088384

Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation

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