Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.

The importance of bone morphogenetic protein 2 (BMP2) in the skeleton is well known. BMP2 is expressed in a variety of tissues during development, growth and healing. In this study we sought to better identify the role of tissue-specific BMP2 during post-natal growth and to determine if BMP2 knockou...

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Autores principales:	Sarah H McBride, Jennifer A McKenzie, Bronwyn S Bedrick, Paige Kuhlmann, Jill D Pasteris, Vicki Rosen, Matthew J Silva
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4fd0986bd2964817852b2f13f9f6516a
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spelling	oai:doaj.org-article:4fd0986bd2964817852b2f13f9f6516a2021-11-18T08:18:52ZLong bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.1932-620310.1371/journal.pone.0096862https://doaj.org/article/4fd0986bd2964817852b2f13f9f6516a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24837969/?tool=EBIhttps://doaj.org/toc/1932-6203The importance of bone morphogenetic protein 2 (BMP2) in the skeleton is well known. BMP2 is expressed in a variety of tissues during development, growth and healing. In this study we sought to better identify the role of tissue-specific BMP2 during post-natal growth and to determine if BMP2 knockout affects the ability of terminally differentiated cells to create high quality bone material. We targeted BMP2 knockout to two differentiated cell types known to express BMP2 during growth and healing, early-stage osteoblasts and their progeny (osterix promoted Cre) and vascular endothelial cells (vascular-endothelial-cadherin promoted Cre). Our objectives were to assess post-natal bone growth, structure and strength. We hypothesized that removal of BMP2 from osteogenic and vascular cells (separately) would result in smaller skeletons with inferior bone material properties. At 12 and 24 weeks of age the osteoblast knockout of BMP2 reduced body weight by 20%, but the vascular knockout had no effect. Analysis of bone in the tibia revealed reductions in cortical and cancellous bone size and volume in the osteoblast knockout, but not in the vascular endothelial knockout. Furthermore, forelimb strength testing revealed a 30% reduction in ultimate force at both 12 and 24 weeks in the osteoblast knockout of BMP2, but no change in the vascular endothelial knockout. Moreover, mechanical strength testing of femurs from osteoblast knockout mice demonstrated an increased Young's modulus (greater than 35%) but decreased post-yield displacement (greater than 50%) at both 12 and 24 weeks of age. In summary, the osteoblast knockout of BMP2 reduced bone size and altered mechanical properties at the whole-bone and material levels. Osteoblast-derived BMP2 has an important role in post-natal skeletal growth, structure and strength, while vascular endothelial-derived BMP2 does not.Sarah H McBrideJennifer A McKenzieBronwyn S BedrickPaige KuhlmannJill D PasterisVicki RosenMatthew J SilvaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e96862 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah H McBride Jennifer A McKenzie Bronwyn S Bedrick Paige Kuhlmann Jill D Pasteris Vicki Rosen Matthew J Silva Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.
description	The importance of bone morphogenetic protein 2 (BMP2) in the skeleton is well known. BMP2 is expressed in a variety of tissues during development, growth and healing. In this study we sought to better identify the role of tissue-specific BMP2 during post-natal growth and to determine if BMP2 knockout affects the ability of terminally differentiated cells to create high quality bone material. We targeted BMP2 knockout to two differentiated cell types known to express BMP2 during growth and healing, early-stage osteoblasts and their progeny (osterix promoted Cre) and vascular endothelial cells (vascular-endothelial-cadherin promoted Cre). Our objectives were to assess post-natal bone growth, structure and strength. We hypothesized that removal of BMP2 from osteogenic and vascular cells (separately) would result in smaller skeletons with inferior bone material properties. At 12 and 24 weeks of age the osteoblast knockout of BMP2 reduced body weight by 20%, but the vascular knockout had no effect. Analysis of bone in the tibia revealed reductions in cortical and cancellous bone size and volume in the osteoblast knockout, but not in the vascular endothelial knockout. Furthermore, forelimb strength testing revealed a 30% reduction in ultimate force at both 12 and 24 weeks in the osteoblast knockout of BMP2, but no change in the vascular endothelial knockout. Moreover, mechanical strength testing of femurs from osteoblast knockout mice demonstrated an increased Young's modulus (greater than 35%) but decreased post-yield displacement (greater than 50%) at both 12 and 24 weeks of age. In summary, the osteoblast knockout of BMP2 reduced bone size and altered mechanical properties at the whole-bone and material levels. Osteoblast-derived BMP2 has an important role in post-natal skeletal growth, structure and strength, while vascular endothelial-derived BMP2 does not.
format	article
author	Sarah H McBride Jennifer A McKenzie Bronwyn S Bedrick Paige Kuhlmann Jill D Pasteris Vicki Rosen Matthew J Silva
author_facet	Sarah H McBride Jennifer A McKenzie Bronwyn S Bedrick Paige Kuhlmann Jill D Pasteris Vicki Rosen Matthew J Silva
author_sort	Sarah H McBride
title	Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.
title_short	Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.
title_full	Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.
title_fullStr	Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.
title_full_unstemmed	Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.
title_sort	long bone structure and strength depend on bmp2 from osteoblasts and osteocytes, but not vascular endothelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/4fd0986bd2964817852b2f13f9f6516a
work_keys_str_mv	AT sarahhmcbride longbonestructureandstrengthdependonbmp2fromosteoblastsandosteocytesbutnotvascularendothelialcells AT jenniferamckenzie longbonestructureandstrengthdependonbmp2fromosteoblastsandosteocytesbutnotvascularendothelialcells AT bronwynsbedrick longbonestructureandstrengthdependonbmp2fromosteoblastsandosteocytesbutnotvascularendothelialcells AT paigekuhlmann longbonestructureandstrengthdependonbmp2fromosteoblastsandosteocytesbutnotvascularendothelialcells AT jilldpasteris longbonestructureandstrengthdependonbmp2fromosteoblastsandosteocytesbutnotvascularendothelialcells AT vickirosen longbonestructureandstrengthdependonbmp2fromosteoblastsandosteocytesbutnotvascularendothelialcells AT matthewjsilva longbonestructureandstrengthdependonbmp2fromosteoblastsandosteocytesbutnotvascularendothelialcells
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Long bone structure and strength depend on BMP2 from osteoblasts and osteocytes, but not vascular endothelial cells.

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