Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis.
The bone-bone marrow interface is an area of the bone marrow microenvironment in which both bone remodeling cells, osteoblasts and osteoclasts, and hematopoietic cells are anatomically juxtaposed. The close proximity of these cells naturally suggests that they interact with one another, but these in...
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doaj-e4debfe3414c41deb8874fd33d8788552020-11-24T21:35:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-11-01411e795510.1371/journal.pone.0007955Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis.April S ChanKristian K JensenDimitris SkokosStephen DotyHannah K LedermanRosandra N KaplanShahin RafiiStefano RivellaDavid LydenThe bone-bone marrow interface is an area of the bone marrow microenvironment in which both bone remodeling cells, osteoblasts and osteoclasts, and hematopoietic cells are anatomically juxtaposed. The close proximity of these cells naturally suggests that they interact with one another, but these interactions are just beginning to be characterized.An Id1(-/-) mouse model was used to assess the role of Id1 in the bone marrow microenvironment. Micro-computed tomography and fracture tests showed that Id1(-/-) mice have reduced bone mass and increased bone fragility, consistent with an osteoporotic phenotype. Osteoclastogenesis and pit formation assays revealed that loss of Id1 increased osteoclast differentiation and resorption activity, both in vivo and in vitro, suggesting a cell autonomous role for Id1 as a negative regulator of osteoclast differentiation. Examination by flow cytometry of the hematopoietic compartment of Id1(-/-) mice showed an increase in myeloid differentiation. Additionally, we found increased expression of osteoclast genes, TRAP, Oscar, and CTSK in the Id1(-/-) bone marrow microenvironment. Lastly, transplantation of wild-type bone marrow into Id1(-/-) mice repressed TRAP, Oscar, and CTSK expression and activity and rescued the hematopoietic and bone phenotype in these mice.In conclusion, we demonstrate an osteoporotic phenotype in Id1(-/-) mice and a mechanism for Id1 transcriptional control of osteoclast-associated genes. Our results identify Id1 as a principal player responsible for the dynamic cross-talk between bone and bone marrow hematopoietic cells.http://europepmc.org/articles/PMC2776978?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
April S Chan Kristian K Jensen Dimitris Skokos Stephen Doty Hannah K Lederman Rosandra N Kaplan Shahin Rafii Stefano Rivella David Lyden |
spellingShingle |
April S Chan Kristian K Jensen Dimitris Skokos Stephen Doty Hannah K Lederman Rosandra N Kaplan Shahin Rafii Stefano Rivella David Lyden Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis. PLoS ONE |
author_facet |
April S Chan Kristian K Jensen Dimitris Skokos Stephen Doty Hannah K Lederman Rosandra N Kaplan Shahin Rafii Stefano Rivella David Lyden |
author_sort |
April S Chan |
title |
Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis. |
title_short |
Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis. |
title_full |
Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis. |
title_fullStr |
Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis. |
title_full_unstemmed |
Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis. |
title_sort |
id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2009-11-01 |
description |
The bone-bone marrow interface is an area of the bone marrow microenvironment in which both bone remodeling cells, osteoblasts and osteoclasts, and hematopoietic cells are anatomically juxtaposed. The close proximity of these cells naturally suggests that they interact with one another, but these interactions are just beginning to be characterized.An Id1(-/-) mouse model was used to assess the role of Id1 in the bone marrow microenvironment. Micro-computed tomography and fracture tests showed that Id1(-/-) mice have reduced bone mass and increased bone fragility, consistent with an osteoporotic phenotype. Osteoclastogenesis and pit formation assays revealed that loss of Id1 increased osteoclast differentiation and resorption activity, both in vivo and in vitro, suggesting a cell autonomous role for Id1 as a negative regulator of osteoclast differentiation. Examination by flow cytometry of the hematopoietic compartment of Id1(-/-) mice showed an increase in myeloid differentiation. Additionally, we found increased expression of osteoclast genes, TRAP, Oscar, and CTSK in the Id1(-/-) bone marrow microenvironment. Lastly, transplantation of wild-type bone marrow into Id1(-/-) mice repressed TRAP, Oscar, and CTSK expression and activity and rescued the hematopoietic and bone phenotype in these mice.In conclusion, we demonstrate an osteoporotic phenotype in Id1(-/-) mice and a mechanism for Id1 transcriptional control of osteoclast-associated genes. Our results identify Id1 as a principal player responsible for the dynamic cross-talk between bone and bone marrow hematopoietic cells. |
url |
http://europepmc.org/articles/PMC2776978?pdf=render |
work_keys_str_mv |
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