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Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency
Immunoreceptor tyrosine-based activation motif (ITAM) signaling mediated by DAP12 or Fcε receptor Iγ chain (FcRγ) have been shown to be critical for osteoclast differentiation and maturation under normal physiological conditions. Their function in pathological conditions is unknown. We studied the r...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895921/ https://www.ncbi.nlm.nih.gov/pubmed/17611621 http://dx.doi.org/10.1371/journal.pone.0000586 |
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author | Wu, Yalei Torchia, James Yao, Wei Lane, Nancy E. Lanier, Lewis L. Nakamura, Mary C. Humphrey, Mary Beth |
author_facet | Wu, Yalei Torchia, James Yao, Wei Lane, Nancy E. Lanier, Lewis L. Nakamura, Mary C. Humphrey, Mary Beth |
author_sort | Wu, Yalei |
collection | PubMed |
description | Immunoreceptor tyrosine-based activation motif (ITAM) signaling mediated by DAP12 or Fcε receptor Iγ chain (FcRγ) have been shown to be critical for osteoclast differentiation and maturation under normal physiological conditions. Their function in pathological conditions is unknown. We studied the role of ITAM signaling during rapid bone remodeling induced by acute estrogen-deficiency in wild-type (WT), DAP12-deficient (DAP12-/-), FcRγ-deficient (FcRγ-/-) and double-deficient (DAP12-/-FcRγ-/-) mice. Six weeks after ovariectomy (OVX), DAP12-/-FcRγ-/- mice showed resistance to lumbar vertebral body (LVB) trabecular bone loss, while WT, DAP12-/- and FcRγ-/- mice had significant LVB bone loss. In contrast, all ITAM adapter-deficient mice responded to OVX with bone loss in both femur and tibia of approximately 40%, relative to basal bone volumes. Only WT mice developed significant cortical bone loss after OVX. In vitro studies showed microenvironmental changes induced by OVX are indispensable for enhanced osteoclast formation and function. Cytokine changes, including TGFβ and TNFα, were able to induce osteoclastogenesis independent of RANKL in BMMs from WT but not DAP12-/- and DAP12-/-FcRγ-/- mice. FSH stimulated RANKL-induced osteoclast differentiation from BMMs in WT, but not DAP12-/- and DAP12-/-FcRγ-/- mice. Our study demonstrates that although ITAM adapter signaling is critical for normal bone remodeling, estrogen-deficiency induces an ITAM adapter-independent bypass mechanism allowing for enhanced osteoclastogenesis and activation in specific bony microenvironments. |
format | Text |
id | pubmed-1895921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-18959212007-07-04 Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency Wu, Yalei Torchia, James Yao, Wei Lane, Nancy E. Lanier, Lewis L. Nakamura, Mary C. Humphrey, Mary Beth PLoS One Research Article Immunoreceptor tyrosine-based activation motif (ITAM) signaling mediated by DAP12 or Fcε receptor Iγ chain (FcRγ) have been shown to be critical for osteoclast differentiation and maturation under normal physiological conditions. Their function in pathological conditions is unknown. We studied the role of ITAM signaling during rapid bone remodeling induced by acute estrogen-deficiency in wild-type (WT), DAP12-deficient (DAP12-/-), FcRγ-deficient (FcRγ-/-) and double-deficient (DAP12-/-FcRγ-/-) mice. Six weeks after ovariectomy (OVX), DAP12-/-FcRγ-/- mice showed resistance to lumbar vertebral body (LVB) trabecular bone loss, while WT, DAP12-/- and FcRγ-/- mice had significant LVB bone loss. In contrast, all ITAM adapter-deficient mice responded to OVX with bone loss in both femur and tibia of approximately 40%, relative to basal bone volumes. Only WT mice developed significant cortical bone loss after OVX. In vitro studies showed microenvironmental changes induced by OVX are indispensable for enhanced osteoclast formation and function. Cytokine changes, including TGFβ and TNFα, were able to induce osteoclastogenesis independent of RANKL in BMMs from WT but not DAP12-/- and DAP12-/-FcRγ-/- mice. FSH stimulated RANKL-induced osteoclast differentiation from BMMs in WT, but not DAP12-/- and DAP12-/-FcRγ-/- mice. Our study demonstrates that although ITAM adapter signaling is critical for normal bone remodeling, estrogen-deficiency induces an ITAM adapter-independent bypass mechanism allowing for enhanced osteoclastogenesis and activation in specific bony microenvironments. Public Library of Science 2007-07-04 /pmc/articles/PMC1895921/ /pubmed/17611621 http://dx.doi.org/10.1371/journal.pone.0000586 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Wu, Yalei Torchia, James Yao, Wei Lane, Nancy E. Lanier, Lewis L. Nakamura, Mary C. Humphrey, Mary Beth Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency |
title | Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency |
title_full | Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency |
title_fullStr | Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency |
title_full_unstemmed | Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency |
title_short | Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency |
title_sort | bone microenvironment specific roles of itam adapter signaling during bone remodeling induced by acute estrogen-deficiency |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895921/ https://www.ncbi.nlm.nih.gov/pubmed/17611621 http://dx.doi.org/10.1371/journal.pone.0000586 |
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