Id1 represses osteoclast-dependent transcription and affects bone formation and hematopoiesis

• Published in: PloS one Vol. 4; no. 11; p. e7955
• Main Authors: Chan, April S, Jensen, Kristian K, Skokos, Dimitris, Doty, Stephen, Lederman, Hannah K, Kaplan, Rosandra N, Rafii, Shahin, Rivella, Stefano, Lyden, David
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.11.2009; Public Library of Science (PLoS)
• Subjects: Analysis; Angiogenesis; Animals; Biocompatibility; Biomedical materials; Bone and Bones - physiology; Bone density; Bone growth; Bone marrow; Bone Marrow Cells - cytology; Bone marrow transplantation; Bone mass; Bone remodeling; Bone resorption; Breast cancer; Children & youth; Colorectal cancer; Computed tomography; Cytometry; Deoxyribonucleic acid; Developmental biology; Developmental Biology/Aging; Developmental Biology/Cell Differentiation; Differentiation; DNA; Female; Flow cytometry; Fragility; Gastric cancer; Gene expression; Gene Expression Regulation; Genes; Hematology; Hematology/Bone Marrow and Stem Cell Transplantation; Hematology/Hematopoiesis; Hematopoiesis; Hematopoietic Stem Cells - cytology; Histology; Homeostasis; Id1 protein; In vivo methods and tests; Inhibitor of Differentiation Protein 1 - metabolism; Laboratories; Male; Metastasis; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mouse devices; Oncology; Osteoblasts; Osteoclastogenesis; Osteoclasts; Osteoclasts - metabolism; Osteogenesis; Osteogenesis - genetics; Osteoporosis; Pancreatic cancer; Pediatrics; Phenotype; Phosphatase; Rodents; Stem cells; Stomach cancer; Transcription; Transcription (Genetics); Transcription factors; Transcription, Genetic; Transplantation; Tumors; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0007955

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.