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Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function

Osteoporosis is one of the most common bone pathologies, which are characterized by a decrease in bone mass. It is well established that bone mass, which results from a balanced bone formation and bone resorption, is regulated by many hormonal, environmental and genetic factors. Here we report that...

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Autores principales: Dacquin, Romain, Domenget, Chantal, Kumanogoh, Atsushi, Kikutani, Hitoshi, Jurdic, Pierre, Machuca-Gayet, Irma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202567/
https://www.ncbi.nlm.nih.gov/pubmed/22046317
http://dx.doi.org/10.1371/journal.pone.0026627
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author Dacquin, Romain
Domenget, Chantal
Kumanogoh, Atsushi
Kikutani, Hitoshi
Jurdic, Pierre
Machuca-Gayet, Irma
author_facet Dacquin, Romain
Domenget, Chantal
Kumanogoh, Atsushi
Kikutani, Hitoshi
Jurdic, Pierre
Machuca-Gayet, Irma
author_sort Dacquin, Romain
collection PubMed
description Osteoporosis is one of the most common bone pathologies, which are characterized by a decrease in bone mass. It is well established that bone mass, which results from a balanced bone formation and bone resorption, is regulated by many hormonal, environmental and genetic factors. Here we report that the immune semaphorin 4D (Sema4D) is a novel factor controlling bone resorption. Sema4D-deficient primary osteoclasts showed impaired spreading, adhesion, migration and resorption due to altered ß3 integrin sub-unit downstream signaling. In apparent accordance with these in vitro results, Sema4D deletion in sexually mature female mice led to a high bone mass phenotype due to defective bone resorption by osteoclasts. Mutant males, however, displayed normal bone mass and the female osteopetrotic phenotype was only detected at the onset of sexual maturity, indicating that, in vivo, this intrinsic osteoclast defect might be overcome in these mice. Using bone marrow cross transplantation, we confirmed that Sema4D controls bone resorption through an indirect mechanism. In addition, we show that Sema4D −/− mice were less fertile than their WT littermates. A decrease in Gnrh1 hypothalamic expression and a reduced number of ovarian follicles can explain this attenuated fertility. Interestingly, ovariectomy abrogated the bone resorption phenotype in Sema4D −/− mice, providing the evidence that the observed high bone mass phenotype is strictly dependent on ovarian function. Altogether, this study reveals that, in vivo, Sema4D is an indirect regulator of bone resorption, which acts via its effect on reproductive function.
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spelling pubmed-32025672011-11-01 Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function Dacquin, Romain Domenget, Chantal Kumanogoh, Atsushi Kikutani, Hitoshi Jurdic, Pierre Machuca-Gayet, Irma PLoS One Research Article Osteoporosis is one of the most common bone pathologies, which are characterized by a decrease in bone mass. It is well established that bone mass, which results from a balanced bone formation and bone resorption, is regulated by many hormonal, environmental and genetic factors. Here we report that the immune semaphorin 4D (Sema4D) is a novel factor controlling bone resorption. Sema4D-deficient primary osteoclasts showed impaired spreading, adhesion, migration and resorption due to altered ß3 integrin sub-unit downstream signaling. In apparent accordance with these in vitro results, Sema4D deletion in sexually mature female mice led to a high bone mass phenotype due to defective bone resorption by osteoclasts. Mutant males, however, displayed normal bone mass and the female osteopetrotic phenotype was only detected at the onset of sexual maturity, indicating that, in vivo, this intrinsic osteoclast defect might be overcome in these mice. Using bone marrow cross transplantation, we confirmed that Sema4D controls bone resorption through an indirect mechanism. In addition, we show that Sema4D −/− mice were less fertile than their WT littermates. A decrease in Gnrh1 hypothalamic expression and a reduced number of ovarian follicles can explain this attenuated fertility. Interestingly, ovariectomy abrogated the bone resorption phenotype in Sema4D −/− mice, providing the evidence that the observed high bone mass phenotype is strictly dependent on ovarian function. Altogether, this study reveals that, in vivo, Sema4D is an indirect regulator of bone resorption, which acts via its effect on reproductive function. Public Library of Science 2011-10-26 /pmc/articles/PMC3202567/ /pubmed/22046317 http://dx.doi.org/10.1371/journal.pone.0026627 Text en Dacquin 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
Dacquin, Romain
Domenget, Chantal
Kumanogoh, Atsushi
Kikutani, Hitoshi
Jurdic, Pierre
Machuca-Gayet, Irma
Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function
title Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function
title_full Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function
title_fullStr Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function
title_full_unstemmed Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function
title_short Control of Bone Resorption by Semaphorin 4D Is Dependent on Ovarian Function
title_sort control of bone resorption by semaphorin 4d is dependent on ovarian function
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202567/
https://www.ncbi.nlm.nih.gov/pubmed/22046317
http://dx.doi.org/10.1371/journal.pone.0026627
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