Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation

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.

Transcriptional regulation of osteopontin gene in vivo by PEBP2αA/CBFA1 and ETS1 in the skeletal tissues

“…We considered that the defective calci®cation in the homozygous (7/7) mice was due to the lack of opn gene expression. Previous reports indicated that PEBP2aA regulated not only the opn gene but also BSP, osteocalcin and type I collagen gene in vitro (Ducy et al, 1997). In the present study, direct regulation of opn gene expression controlled by PEBP2aA and ETS1 was shown.…”

Pax3 activation promotes the differentiation of mesenchymal stem cells toward the myogenic lineage

“…Conversely, with aging, commitment of murine MSCs to the adipogenic lineage is enhanced at the expense of osteogenesis [40], a phenotype which correlates with increased levels of PPARγ-2 [40]. While PPARγ-2 is essential to drive adipogenesis from MSCs [38,43], Runx2 (Cbfa1) seems to be the key player for osteoblast differentiation [41][42][43]. Our results show that Pax3 overexpression blocks adipogenesis, osteogenesis, and chondrogenesis potentially by inhibiting PPARγ-2 and Cbfa-1.…”

c-Jun N-terminal kinase 1 negatively regulates osteoblastic differentiation induced by BMP2 via phosphorylation of Runx2 at Ser104

“…Luciferase assay was performed by using the Dual Luciferase Reporter Assay kit, according to the manufacturer's protocol (Promega, Madison, WI, USA). Briefly, C2C12 cells were cultured in serum-free medium in 96-well assay plates and transfected with 200 ng/well reporter plasmid, p6OSE2-Luc or p6mutOSE2-Luc, (34) plus 20 ng/well control plasmid, Renilla luciferase plasmid (pRL-TK). After 24 hours of incubation, cells were replenished with fresh medium containing vehicle, BMP2 alone, or BMP2 plus 5 mM SP600125 (Calbiochem).…”