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DAP12 Overexpression Induces Osteopenia and Impaired Early Hematopoiesis

ITAM-bearing transmembrane signaling adaptors such as DAP12 and FcRγ are important players in bone homeostasis, but their precise role and functions are still unknown. It has been shown that osteoclast differentiation results from the integration of the RANK and of the DAP12 and FcRγ signaling pathw...

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Autores principales: Despars, Geneviève, Pandruvada, Subramanya N. M., Anginot, Adrienne, Domenget, Chantal, Jurdic, Pierre, Mazzorana, Marlène
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679081/
https://www.ncbi.nlm.nih.gov/pubmed/23776468
http://dx.doi.org/10.1371/journal.pone.0065297
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author Despars, Geneviève
Pandruvada, Subramanya N. M.
Anginot, Adrienne
Domenget, Chantal
Jurdic, Pierre
Mazzorana, Marlène
author_facet Despars, Geneviève
Pandruvada, Subramanya N. M.
Anginot, Adrienne
Domenget, Chantal
Jurdic, Pierre
Mazzorana, Marlène
author_sort Despars, Geneviève
collection PubMed
description ITAM-bearing transmembrane signaling adaptors such as DAP12 and FcRγ are important players in bone homeostasis, but their precise role and functions are still unknown. It has been shown that osteoclast differentiation results from the integration of the RANK and of the DAP12 and FcRγ signaling pathways. DAP12-deficient mice suffer from a mild osteopetrosis and culture of their bone marrow cells in the presence of M-CSF and RANKL, fails to give rise to multinucleated osteoclasts. Here, we report that mice overexpressing human DAP12 have an osteopenic bone phenotype due to an increased number of osteoclasts on the surface of trabecular and cortical bone. This enhanced number of osteoclasts is associated with an increased number of proliferating myeloid progenitors in Tg-hDAP12 mice. It is concomitant with an arrest of B cell development at the Pre-Pro B/Pre B stage in the bone marrow of Tg-hDAP12 mice and important decrease of follicular and marginal B cells in the spleen of these animals. Our data show that the overexpression of DAP12 results in both increased osteoclastogenesis and impaired hematopoiesis underlining the relationship between bone homeostasis and hematopoiesis.
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spelling pubmed-36790812013-06-17 DAP12 Overexpression Induces Osteopenia and Impaired Early Hematopoiesis Despars, Geneviève Pandruvada, Subramanya N. M. Anginot, Adrienne Domenget, Chantal Jurdic, Pierre Mazzorana, Marlène PLoS One Research Article ITAM-bearing transmembrane signaling adaptors such as DAP12 and FcRγ are important players in bone homeostasis, but their precise role and functions are still unknown. It has been shown that osteoclast differentiation results from the integration of the RANK and of the DAP12 and FcRγ signaling pathways. DAP12-deficient mice suffer from a mild osteopetrosis and culture of their bone marrow cells in the presence of M-CSF and RANKL, fails to give rise to multinucleated osteoclasts. Here, we report that mice overexpressing human DAP12 have an osteopenic bone phenotype due to an increased number of osteoclasts on the surface of trabecular and cortical bone. This enhanced number of osteoclasts is associated with an increased number of proliferating myeloid progenitors in Tg-hDAP12 mice. It is concomitant with an arrest of B cell development at the Pre-Pro B/Pre B stage in the bone marrow of Tg-hDAP12 mice and important decrease of follicular and marginal B cells in the spleen of these animals. Our data show that the overexpression of DAP12 results in both increased osteoclastogenesis and impaired hematopoiesis underlining the relationship between bone homeostasis and hematopoiesis. Public Library of Science 2013-06-11 /pmc/articles/PMC3679081/ /pubmed/23776468 http://dx.doi.org/10.1371/journal.pone.0065297 Text en © 2013 Despars 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
Despars, Geneviève
Pandruvada, Subramanya N. M.
Anginot, Adrienne
Domenget, Chantal
Jurdic, Pierre
Mazzorana, Marlène
DAP12 Overexpression Induces Osteopenia and Impaired Early Hematopoiesis
title DAP12 Overexpression Induces Osteopenia and Impaired Early Hematopoiesis
title_full DAP12 Overexpression Induces Osteopenia and Impaired Early Hematopoiesis
title_fullStr DAP12 Overexpression Induces Osteopenia and Impaired Early Hematopoiesis
title_full_unstemmed DAP12 Overexpression Induces Osteopenia and Impaired Early Hematopoiesis
title_short DAP12 Overexpression Induces Osteopenia and Impaired Early Hematopoiesis
title_sort dap12 overexpression induces osteopenia and impaired early hematopoiesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679081/
https://www.ncbi.nlm.nih.gov/pubmed/23776468
http://dx.doi.org/10.1371/journal.pone.0065297
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