The bone-specific expression of Runx2 oscillates during the cell cycle to support a G1-related antiproliferative function in osteoblasts
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center
Medical Subject Headings
Animals; Cell Cycle; Cell Division; Cell Line; Cell Line, Transformed; Cell Nucleus; Core Binding Factor Alpha 1 Subunit; DNA-Binding Proteins; G1 Phase; *Gene Expression Regulation; Humans; Kinetics; Mice; Mitosis; Osteoblasts; Osteosarcoma; Protein Isoforms; RNA, Messenger; Rats; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factor AP-2; Transcription Factors; Transfection; Tumor Cells, Cultured
Life Sciences | Medicine and Health Sciences
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.
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Citation: J Biol Chem. 2005 May 27;280(21):20274-85. Epub 2005 Mar 21. Link to article on publisher's site
DOI of Published Version
The Journal of biological chemistry
Galindo, Mario; Pratap, Jitesh; Young, Daniel W.; Hovhannisyan, Hayk; Im, Hee-Jeong; Choi, Je-Yong; Lian, Jane B.; Stein, Janet L.; Stein, Gary S.; and Van Wijnen, Andre J., "The bone-specific expression of Runx2 oscillates during the cell cycle to support a G1-related antiproliferative function in osteoblasts" (2005). GSBS Student Publications. 366.