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


RESULTS
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.


CONCLUSIONS
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.
Chan
April S
AS
Department of Pediatrics, Weill Cornell Medical College, New York, New York, United States of America.
Jensen
Kristian K
KK
Skokos
Dimitris
D
Doty
Stephen
S
Lederman
Hannah K
HK
Kaplan
Rosandra N
RN
Rafii
Shahin
S
Rivella
Stefano
S
Lyden
David
D
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001842:Bone and Bones / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics*; D010641:Phenotype; D014158:Transcription, Genetic
C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1