Title
The bone-specific expression of Runx2 oscillates during the cell cycle to support a G1-related antiproliferative function in osteoblasts
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Cell Biology and Cancer Center
Publication Date
2005-03-23
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
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.
DOI of Published Version
10.1074/jbc.M413665200
Source
J Biol Chem. 2005 May 27;280(21):20274-85. Epub 2005 Mar 21. Link to article on publisher's site
Journal/Book/Conference Title
The Journal of biological chemistry
Related Resources
PubMed ID
15781466
Repository Citation
Galindo M, Pratap J, Young DW, Hovhannisyan H, Im H, Choi J, Lian JB, Stein JL, Stein GS, Van Wijnen AJ. (2005). The bone-specific expression of Runx2 oscillates during the cell cycle to support a G1-related antiproliferative function in osteoblasts. GSBS Student Publications. https://doi.org/10.1074/jbc.M413665200. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/366