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Transgenic Overexpression of Ephrin B1 in Bone Cells Promotes Bone Formation and an Anabolic Response to Mechanical Loading in Mice

To test if ephrin B1 overexpression enhances bone mass, we generated transgenic mice overexpressing ephrin B1 under the control of a 3.6 kb rat collagen 1A1 promoter (Col3.6-Tg(efnb1)). Col3.6-Tg(efnb1) mice express 6-, 12- and 14-fold greater levels of full-length ephrin B1 protein in bone marrow s...

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Autores principales: Cheng, Shaohong, Kesavan, Chandrasekhar, Mohan, Subburaman, Qin, Xuezhong, Alarcon, Catrina M., Wergedal, Jon, Xing, Weirong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708903/
https://www.ncbi.nlm.nih.gov/pubmed/23874863
http://dx.doi.org/10.1371/journal.pone.0069051
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author Cheng, Shaohong
Kesavan, Chandrasekhar
Mohan, Subburaman
Qin, Xuezhong
Alarcon, Catrina M.
Wergedal, Jon
Xing, Weirong
author_facet Cheng, Shaohong
Kesavan, Chandrasekhar
Mohan, Subburaman
Qin, Xuezhong
Alarcon, Catrina M.
Wergedal, Jon
Xing, Weirong
author_sort Cheng, Shaohong
collection PubMed
description To test if ephrin B1 overexpression enhances bone mass, we generated transgenic mice overexpressing ephrin B1 under the control of a 3.6 kb rat collagen 1A1 promoter (Col3.6-Tg(efnb1)). Col3.6-Tg(efnb1) mice express 6-, 12- and 14-fold greater levels of full-length ephrin B1 protein in bone marrow stromal cells, calvarial osteoblasts, and osteoclasts, respectively. The long bones of both genders of Col3.6-Tg(efnb1) mice have increased trabecular bone volume, trabecular number, and trabecular thickness and decreased trabecular separation. Enhanced bone formation and decreased bone resorption contributed to this increase in trabecular bone mass in Col3.6-Tg(efnb1) mice. Consistent with these findings, our in vitro studies showed that overexpression of ephrin B1 increased osteoblast differentiation and mineralization, osterix and collagen 1A1 expression in bone marrow stromal cells. Interaction of ephrin B1 with soluble clustered EphB2-Fc decreased osteoclast precursor differentiation into multinucleated cells. Furthermore, we demonstrated that the mechanical loading-induced increase in EphB2 expression and newly formed bone were significantly greater in the Col3.6-Tg(efnb1) mice than in WT littermate controls. Our findings that overexpression of ephrin B1 in bone cells enhances bone mass and promotes a skeletal anabolic response to mechanical loading suggest that manipulation of ephrin B1 actions in bone may provide a means to sensitize the skeleton to mechanical strain to stimulate new bone formation.
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spelling pubmed-37089032013-07-19 Transgenic Overexpression of Ephrin B1 in Bone Cells Promotes Bone Formation and an Anabolic Response to Mechanical Loading in Mice Cheng, Shaohong Kesavan, Chandrasekhar Mohan, Subburaman Qin, Xuezhong Alarcon, Catrina M. Wergedal, Jon Xing, Weirong PLoS One Research Article To test if ephrin B1 overexpression enhances bone mass, we generated transgenic mice overexpressing ephrin B1 under the control of a 3.6 kb rat collagen 1A1 promoter (Col3.6-Tg(efnb1)). Col3.6-Tg(efnb1) mice express 6-, 12- and 14-fold greater levels of full-length ephrin B1 protein in bone marrow stromal cells, calvarial osteoblasts, and osteoclasts, respectively. The long bones of both genders of Col3.6-Tg(efnb1) mice have increased trabecular bone volume, trabecular number, and trabecular thickness and decreased trabecular separation. Enhanced bone formation and decreased bone resorption contributed to this increase in trabecular bone mass in Col3.6-Tg(efnb1) mice. Consistent with these findings, our in vitro studies showed that overexpression of ephrin B1 increased osteoblast differentiation and mineralization, osterix and collagen 1A1 expression in bone marrow stromal cells. Interaction of ephrin B1 with soluble clustered EphB2-Fc decreased osteoclast precursor differentiation into multinucleated cells. Furthermore, we demonstrated that the mechanical loading-induced increase in EphB2 expression and newly formed bone were significantly greater in the Col3.6-Tg(efnb1) mice than in WT littermate controls. Our findings that overexpression of ephrin B1 in bone cells enhances bone mass and promotes a skeletal anabolic response to mechanical loading suggest that manipulation of ephrin B1 actions in bone may provide a means to sensitize the skeleton to mechanical strain to stimulate new bone formation. Public Library of Science 2013-07-11 /pmc/articles/PMC3708903/ /pubmed/23874863 http://dx.doi.org/10.1371/journal.pone.0069051 Text en © 2013 Cheng et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Cheng, Shaohong
Kesavan, Chandrasekhar
Mohan, Subburaman
Qin, Xuezhong
Alarcon, Catrina M.
Wergedal, Jon
Xing, Weirong
Transgenic Overexpression of Ephrin B1 in Bone Cells Promotes Bone Formation and an Anabolic Response to Mechanical Loading in Mice
title Transgenic Overexpression of Ephrin B1 in Bone Cells Promotes Bone Formation and an Anabolic Response to Mechanical Loading in Mice
title_full Transgenic Overexpression of Ephrin B1 in Bone Cells Promotes Bone Formation and an Anabolic Response to Mechanical Loading in Mice
title_fullStr Transgenic Overexpression of Ephrin B1 in Bone Cells Promotes Bone Formation and an Anabolic Response to Mechanical Loading in Mice
title_full_unstemmed Transgenic Overexpression of Ephrin B1 in Bone Cells Promotes Bone Formation and an Anabolic Response to Mechanical Loading in Mice
title_short Transgenic Overexpression of Ephrin B1 in Bone Cells Promotes Bone Formation and an Anabolic Response to Mechanical Loading in Mice
title_sort transgenic overexpression of ephrin b1 in bone cells promotes bone formation and an anabolic response to mechanical loading in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708903/
https://www.ncbi.nlm.nih.gov/pubmed/23874863
http://dx.doi.org/10.1371/journal.pone.0069051
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