Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis Journal Article
| Authors: | Chan, A. S.; Jensen, K. K.; Skokos, D.; Doty, S.; Lederman, H. K.; Kaplan, R. N.; Rafii, S.; Rivella, S.; Lyden, D. |
| Article Title: | Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis |
| Abstract: | Background: 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. Methodology/Principal Findings: An Id1<sup>-/-</sup> mouse model was used to assess the role of Id1 in the bone marrow microenvironment. Micro-computed tomography and fracture tests showed that Id1<sup>-/-</sup> 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<sup>-/-</sup> mice showed an increase in myeloid differentiation. Additionally, we found increased expression of osteoclast genes, TRAP, Oscar, and CTSK in the Id<sup>-/2</sup> bone marrow microenvironment. Lastly, transplantation of wild-type bone marrow into Id1<sup>-/-</sup> mice repressed TRAP, Oscar, and CTSK expression and activity and rescued the hematopoietic and bone phenotype in these mice. Conclusions/Significance: In conclusion, we demonstrate an osteoporotic phenotype in Id1<sup>-/-</sup> 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. © 2009 Chan et al. |
| Keywords: | controlled study; unclassified drug; genetics; nonhuman; flow cytometry; animal cell; mouse; phenotype; animal; cytology; metabolism; animals; mice; bone marrow cells; mus; gene expression; inhibitor of differentiation 1; cell protein; animal experiment; gene function; genetic transcription; cell differentiation; transcription, genetic; mice, inbred c57bl; physiology; transgenic mouse; c57bl mouse; mice, transgenic; gene expression regulation; regulatory mechanism; bone; hematopoietic stem cells; hematopoiesis; cathepsin k; oscar; thrombin receptor activating peptide; idb1 protein, mouse; bone fragility; bone marrow cell; bone mass; micro-computed tomography; microenvironment; molecular interaction; ossification; osteoclast; osteoporosis; bone development; hematopoietic stem cell; bone and bones; inhibitor of differentiation protein 1; osteoclasts; osteogenesis |
| Journal Title: | PLoS ONE |
| Volume: | 4 |
| Issue: | 11 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2009-11-24 |
| Start Page: | e7955 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0007955 |
| PUBMED: | 19956687 |
| PROVIDER: | scopus |
| PMCID: | PMC2776978 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "Art. No.: e7955" - "Source: Scopus" |
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