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Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency

Overview of attention for article published in PLOS ONE, July 2007
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Title
Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency
Published in
PLOS ONE, July 2007
DOI 10.1371/journal.pone.0000586
Pubmed ID
Authors

Yalei Wu, James Torchia, Wei Yao, Nancy E. Lane, Lewis L. Lanier, Mary C. Nakamura, Mary Beth Humphrey

Abstract

Immunoreceptor tyrosine-based activation motif (ITAM) signaling mediated by DAP12 or Fcepsilon receptor Igamma chain (FcRgamma) 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-/-), FcRgamma-deficient (FcRgamma-/-) and double-deficient (DAP12-/-FcRgamma-/-) mice. Six weeks after ovariectomy (OVX), DAP12-/-FcRgamma-/- mice showed resistance to lumbar vertebral body (LVB) trabecular bone loss, while WT, DAP12-/- and FcRgamma-/- 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 TGFbeta and TNFalpha, were able to induce osteoclastogenesis independent of RANKL in BMMs from WT but not DAP12-/- and DAP12-/-FcRgamma-/- mice. FSH stimulated RANKL-induced osteoclast differentiation from BMMs in WT, but not DAP12-/- and DAP12-/-FcRgamma-/- 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.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 23%
Researcher 5 19%
Professor > Associate Professor 3 12%
Professor 2 8%
Other 2 8%
Other 3 12%
Unknown 5 19%
Readers by discipline Count As %
Agricultural and Biological Sciences 7 27%
Medicine and Dentistry 6 23%
Biochemistry, Genetics and Molecular Biology 2 8%
Neuroscience 2 8%
Social Sciences 1 4%
Other 2 8%
Unknown 6 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 October 2007.
All research outputs
#15,240,835
of 22,660,862 outputs
Outputs from PLOS ONE
#129,810
of 193,497 outputs
Outputs of similar age
#58,965
of 68,374 outputs
Outputs of similar age from PLOS ONE
#155
of 176 outputs
Altmetric has tracked 22,660,862 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 176 others from the same source and published within six weeks on either side of this one. This one is in the 7th percentile – i.e., 7% of its contemporaries scored the same or lower than it.