Journal ArticleDOI
Runt Homology Domain Proteins in Osteoblast Differentiation: AML3/CBFA1 Is a Major Component of a Bone-Specific Complex
Chaitali Banerjee,Laura R. McCabe,Je-Yong Choi,Scott W. Hiebert,Janet L. Stein,Gary S. Stein,Jane B. Lian +6 more
TLDR
It is demonstrated that in primary rat osteoblasts AML‐3 is the AML family member present in the osteoblast‐specific complex and that the activity of rhd proteins is required for completion of osteobasts differentiation.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.read more
Citations
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Canonical WNT Signaling Promotes Osteogenesis by Directly Stimulating Runx2 Gene Expression
Tripti Gaur,Christopher J. Lengner,Hayk Hovhannisyan,Ramesh A. Bhat,Peter V.N. Bodine,Barry S. Komm,Amjad Javed,Andre J. van Wijnen,Janet L. Stein,Gary S. Stein,Jane B. Lian +10 more
TL;DR: It is proposed that WNT/TCF1 signaling, like bone morphogenetic protein/transforming growth factor-β signaling, activates Runx2 gene expression in mesenchymal cells for the control of osteoblast differentiation and skeletal development.
Journal ArticleDOI
Runx2 is a common target of transforming growth factor beta1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12.
Kyeong-Sook Lee,Hyun-Jung Kim,Qing-Lin Li,Xin-Zi Chi,Chisato Ueta,Toshihisa Komori,John M. Wozney,Eung-Gook Kim,Je-Young Choi,Hyun-Mo Ryoo,Suk-Chul Bae +10 more
TL;DR: The results indicate that Runx 2 is a major target gene shared by TGF-β and BMP signaling pathways and that the coordinated action of Runx2 and B MP-activated Smads leads to the induction of osteoblast-specific gene expression in C2C12 cells.
Journal ArticleDOI
Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1.
TL;DR: In this article, the authors reviewed the regulation of osteoblast differentiation mediated by the local factors such as bone morphogenetic proteins (BMPs) and hedgehogs and the transcription factor, core-binding factor alpha-1 (Cbfa1).
Journal ArticleDOI
Regulation of bone development and extracellular matrix protein genes by RUNX2.
TL;DR: RUNX2 directs pluripotent mesenchymal cells to the osteoblast lineage, triggers the expression of major bone matrix protein genes, and keeps the osteoblasts in an immature stage, but does not play a major role in the maintenance of theexpression of Col1a1 or Bglap in mature osteoblast.
Journal ArticleDOI
Isolation and characterization of MC3T3-E1 preosteoblast subclones with distinct in vitro and in vivo differentiation/mineralization potential.
Dian Wang,Kurt D. Christensen,Kanwal Chawla,Guozhi Xiao,Paul H. Krebsbach,Renny T. Franceschi +5 more
TL;DR: Interestingly, subclones with both high and low differentiation potential produced similar amounts of collagen in culture and expressed comparable basal levels of mRNA encoding Osf2/Cbfa1, an osteoblast‐related transcription factor, and there was no clear relationship between levels of this message and induction of mRNAs for other differentiation markers.
References
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Journal ArticleDOI
AML1, the Target of Multiple Chromosomal Translocations in Human Leukemia, Is Essential for Normal Fetal Liver Hematopoiesis
TL;DR: The results suggest that AML1-regulated target genes are essential for definitive hematopoiesis of all lineages, and that this defect was intrinsic to the stem cells in that AMl1-/-ES cells failed to contribute to hematocerosis in chimeric animals.
Journal ArticleDOI
Progressive development of the rat osteoblast phenotype in vitro: Reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix
Thomas A. Owen,Michael A. Aronow,Victoria Shalhoub,Leesa M. Barone,Laurens G. Wilming,Melissa S. Tassinari,Mary Beth Kennedy,Shirwin M. Pockwinse,Jane B. Lian,Gary S. Stein +9 more
TL;DR: The relationship of cell proliferation to the temporal expression of genes characterizing a developmental sequence associated with bone cell differentiation was examined in primary diploid cultures of fetal calvarial derived osteoblasts by the combined use of autoradiography, histochemistry, biochemistry, and mRNA assays of osteoblast cell growth and phenotypic genes.
Progressive Development of the Rat Osteoblast Phenotype In Vitro: Reciprocal Relationships in Expression of Genes Associated With Osteoblast Proliferation and Differentiation During Formation of the
Thomas A. Owen,Michael A. Aronow,Victoria Shalhoub,Leesa M. Barone,Laurens G. Wilming,Melissa S. Tassinari,Mary Beth Kennedy,Jane B. Lian,Gary S. Stein +8 more
TL;DR: In this article, the relationship of cell proliferation to the temporal expression of genes characterizing a developmental sequence associated with bone cell differentiation was examined in primary diploid cultures of fetal calvarial derived osteoblasts by the combined use of autoradiography, histochemistry, biochemistry, and mRNA assays of osteoblast cell growth and phenotypic genes.
Journal ArticleDOI
Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis.
TL;DR: The CBFA2 (AML1) gene encodes a DNA-binding subunit of the heterodimeric core-binding factor, which significantly reduces the number of progenitors for erythroid and myeloid cells.
Journal ArticleDOI
PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene.
Eiko Ogawa,Mitsuo Maruyama,Hiroshi Kagoshima,Manabu Inuzuka,Jie Lu,Masanobu Satake,Katsuya Shigesada,Yoshiaki Ito +7 more
TL;DR: Evidence indicated that PEBP2 functions as a transcriptional activator and is involved in regulation of T-cell-specific gene expression, a newly discovered family of transcription factor.