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Runx1 Regulates Myeloid Precursor Differentiation Into Osteoclasts Without Affecting Differentiation Into Antigen Presenting or Phagocytic Cells in Both Males and Females

Overview of attention for article published in Endocrinology, August 2016
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Title
Runx1 Regulates Myeloid Precursor Differentiation Into Osteoclasts Without Affecting Differentiation Into Antigen Presenting or Phagocytic Cells in Both Males and Females
Published in
Endocrinology, August 2016
DOI 10.1210/en.2015-2037
Pubmed ID
Authors

David N. Paglia, Xiaochuan Yang, Judith Kalinowski, Sandra Jastrzebski, Hicham Drissi, Joseph Lorenzo

Abstract

Runx1, a master-regulator of hematopoiesis, is expressed in preosteoclasts. Previously, we evaluated the bone phenotype of CD11b-Cre Runx1(fl/fl) mice and demonstrated enhanced osteoclasts and decreased bone mass in males. However, assessment of the effects of Runx1 deletion in female osteoclast precursors was impossible with this model. Moreover, the role of Runx1 in myeloid cell differentiation into other lineages is unknown. Therefore, we generated LysM-Cre Runx1(fl/fl) mice, which delete Runx1 equally (approx. 80% deletion) in myeloid precursor cells from both sexes and examined the capacity of these cells to differentiate into osteoclasts, phagocytic and antigen presenting cells. Both female and male LysM-Cre Runx1(fl/fl) mice had decreased trabecular bone mass (72% decrease in BV/TV), increased osteoclast number (2-3X) (p<0.05) without alteration of osteoblast histomorphometric indicies. We also demonstrated that loss of Runx1 in pluripotential myeloid precursors with LysM-Cre did not alter the number of myeloid precursor cells in bone marrow or their ability to differentiate into phagocytizing or antigen presenting cells. This study demonstrates that abrogation of Runx1 in multipotential myeloid precursor cells significantly and specifically enhanced the ability of RANKL to stimulate osteoclast formation and fusion in female and male mice without affecting other myeloid cell fates. In turn, increased osteoclast activity in LysM-Cre Runx1(fl/fl) mice likely contributed to a decrease in bone mass. These dramatic effects were not due to increased osteoclast precursors in the deleted mutants and argue that inhibition of Runx1 in multipotential myeloid precursor cells is important for osteoclast formation and function.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 4 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 4 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 1 25%
Student > Doctoral Student 1 25%
Unknown 2 50%
Readers by discipline Count As %
Agricultural and Biological Sciences 1 25%
Immunology and Microbiology 1 25%
Unknown 2 50%

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 09 June 2016.
All research outputs
#9,948,139
of 12,426,426 outputs
Outputs from Endocrinology
#6,381
of 7,188 outputs
Outputs of similar age
#187,281
of 268,554 outputs
Outputs of similar age from Endocrinology
#45
of 88 outputs
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