Abstract
The osteoblast is the bone-forming cell. The molecular basis of osteoblast-specific gene expression and differentiation is unknown. We previously identified an osteoblast-specific cis-acting element, termed OSE2, in the Osteocalcin promoter. We have now cloned the cDNA encoding Osf2/Cbfa1, the protein that binds to OSE2. Osf2/Cbfa1 expression is initiated in the mesenchymal condensations of the developing skeleton, is strictly restricted to cells of the osteoblast lineage thereafter, and is regulated by BMP7 and vitamin D3. Osf2/Cbfa1 binds to and regulates the expression of multiple genes expressed in osteoblasts. Finally, forced expression of Osf2/Cbfa1 in nonosteoblastic cells induces the expression of the principal osteoblast- specific genes. This study identifies Osf2/Cbfa1 as an osteoblast-specific transcription factor and as a regulator of osteoblast differentiation.
| Original language | English |
|---|---|
| Pages (from-to) | 747-754 |
| Number of pages | 8 |
| Journal | Cell |
| Volume | 89 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 30 1997 |
Bibliographical note
Funding Information:We thank B. R. Olsen and M. J. Owen for sharing unpublished data. We are grateful to B. Bruce for expert technical assistance, to B. de Crombrugghe, G. Eichele, S. Hiebert, Y. Ito, K. Sampath, and M. Young for reagents, and to H. Bellen and L. Etkin for critical reading of the manuscript. G. K. thanks G. Rodan for his advice. This work was supported by a Basic Science Award of the March of Dimes Foundation (IFY 92–0871) and a grant from the National Institute of Health (DE-11290) to G. K. Fellowships from the Arthritis Foundation and from the Roussel Scientific Institute supported P. D. and V. G., respectively.
Funding
We thank B. R. Olsen and M. J. Owen for sharing unpublished data. We are grateful to B. Bruce for expert technical assistance, to B. de Crombrugghe, G. Eichele, S. Hiebert, Y. Ito, K. Sampath, and M. Young for reagents, and to H. Bellen and L. Etkin for critical reading of the manuscript. G. K. thanks G. Rodan for his advice. This work was supported by a Basic Science Award of the March of Dimes Foundation (IFY 92–0871) and a grant from the National Institute of Health (DE-11290) to G. K. Fellowships from the Arthritis Foundation and from the Roussel Scientific Institute supported P. D. and V. G., respectively.
ASJC Scopus Subject Areas
- General Biochemistry,Genetics and Molecular Biology