Document Detail

The bone-specific expression of Runx2 oscillates during the cell cycle to support a G1-related antiproliferative function in osteoblasts.
MedLine Citation:
PMID:  15781466     Owner:  NLM     Status:  MEDLINE    
The Runx2 (CBFA1/AML3/PEBP2alphaA) transcription factor promotes skeletal cell differentiation, but it also has a novel cell growth regulatory activity in osteoblasts. We addressed here whether Runx2 activity is functionally linked to cell cycle-related mechanisms that control normal osteoblast proliferation and differentiation. We found that the levels of Runx2 gene transcription, mRNA and protein, are each up-regulated with cessation of cell growth (i.e. G(0)/G(1) transition) in preconfluent MC3T3 osteoblastic cells that do not yet express mature bone phenotypic gene expression. Cell growth regulation of Runx2 is also observed in primary calvarial osteoblasts and other osteoblastic cells with relatively normal cell growth characteristics, but not in osteosarcoma cells (e.g. SAOS-2 and ROS17/2.8). Runx2 levels are cell cycle-regulated in MC3T3 cells with respect to the G(1)/S and M/G(1) transitions: oscillates from maximal expression levels during early G(1) to minimal levels during early S phase and mitosis. However, in normal or immortalized (e.g. ATDC5) chondrocytic cells, Runx2 expression is suppressed during quiescence, and Runx2 levels are not regulated during G(1) and S phase in ATDC5 cells. Antisense or small interfering RNA-mediated reduction of the low physiological levels of Runx2 in proliferating MC3T3 cells does not accelerate cell cycle progression. However, forced expression of Runx2 suppresses proliferation of MC3T3 preosteoblasts or C2C12 mesenchymal cells which have osteogenic potential. Forced elevation of Runx2 in synchronized MC3T3 cells causes a delay in G(1). We propose that Runx2 levels and function are biologically linked to a cell growth-related G(1) transition in osteoblastic cells.
Mario Galindo; Jitesh Pratap; Daniel W Young; Hayk Hovhannisyan; Hee-Jeong Im; Je-Yong Choi; Jane B Lian; Janet L Stein; Gary S Stein; Andre J van Wijnen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-03-21
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-05-23     Completed Date:  2005-08-15     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  20274-85     Citation Subset:  IM    
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
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MeSH Terms
Cell Cycle / physiology*
Cell Division / physiology*
Cell Line
Cell Line, Transformed
Cell Nucleus / chemistry
Core Binding Factor Alpha 1 Subunit
DNA-Binding Proteins / analysis,  genetics*,  physiology*
G1 Phase / physiology
Gene Expression Regulation*
Osteoblasts / chemistry,  cytology*,  metabolism
Osteosarcoma / metabolism
Protein Isoforms / genetics
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factor AP-2
Transcription Factors / analysis,  genetics*,  physiology*
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Core Binding Factor Alpha 1 Subunit; 0/DNA-Binding Proteins; 0/Protein Isoforms; 0/RNA, Messenger; 0/RUNX2 protein, human; 0/Runx2 protein, mouse; 0/Runx2 protein, rat; 0/Transcription Factor AP-2; 0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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