Title

Runt homology domain proteins in osteoblast differentiation: AML3/CBFA1 is a major component of a bone-specific complex

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology

Publication Date

1997-07-01

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The AML/CBFA family of runt homology domain (rhd) transcription factors regulates expression of mammalian genes of the hematopoietic lineage. AML1, AML2 and AML3 are the three AML genes identified to date which influence myeloid cell growth and differentiation. Recently AML-related proteins were identified in an osteoblast-specific promoter binding complex that functionally modulates bone-restricted transcription of the osteocalcin gene. In the present study we demonstrate that in primary rat osteoblasts AML-3 is the AML family member present in the osteoblast-specific complex. Antibody specific for AML-3 completely supershifts this complex, in contrast to antibodies with specificity for AML-1 or AML-2, AML-3 is present as a single 5.4 kb transcript in bone tissues. To establish the functional involvement of AML factors in osteoblast differentiation, we pursued antisense strategies to alter expression of rhd genes. Treatment of osteoblast cultures with rhd antisense oligonucleotides significantly decreased three parameters which are linked to differentiation of normal diploid osteoblasts: the representation of alkaline phosphatase-positive cells, osteocalcin production, and the formation of mineralized nodules. Our findings indicate that AML-3 is a key transcription factor in bone cells and that the activity of rhd proteins is required for completion of osteoblast differentiation.

DOI of Published Version

10.1002/(SICI)1097-4644(19970701)66:1<1::AID-JCB1>3.0.CO;2-V

Source

J Cell Biochem. 1997 Jul 1;66(1):1-8.

Journal/Book/Conference Title

Journal of cellular biochemistry

Related Resources

Link to article in PubMed

PubMed ID

9215522

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