Biopolymers and cell. 2010; 26 (4): 273 - 278
Bone-specific master transcription factor Runx2 regulates signaling and metabolism related programs in osteoprogenitors
N. M. Teplyuk1, 2, V. I. Teplyuk2
1University of Massachusetts Medical School 55, Lake Ave North, 01655, Worcester, MA, USA
2Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine 150, Zabolotnogo str., Kiev, Ukraine, 03680
Aim. Runx2 (AML3) transcription factor is the key regulator of osteoblastic lineage progression and isindispensable for the formation of mineral bones. Runx2 expression increases during differentiation of osteoblasts to induce osteoblast-specific genes necessary for the production and deposition of bone mineral matrix. However, Runx2 is also expressed at a lower level in early osteoprogenitors, where its function is less understood. Here we study how Runx2 determines the early stages of osteoblastic commitment using the model system of Runx2 re-introduction in mouse calvaria cells with Runx2 null background. Method. Affymetrix analysis, Western blot analysis and quantitative real-time reverse transcriptase PCR (qRT-PCR) analysis were employed. Results. Gene expression profiling by Affymetrix microarrays revealed that along with the induction of extracellular matrix and bone mineral deposition related phenotypic markers, Runx2 regulates several cell programs related to signaling and metabolism in the early osteoprogenitors. Particularly, Runx2 regulates transcription of genes involved in G-protein coupled signaling network, FGF and BMP/TGF beta signaling pathways and in biogenesis and metabolism pathways of steroid hormones. Conclusion. The data indicate that the lineage specific program, regulated by the master regulatory transcription factor, includes the regulation of cellular signaling and metabolism which may allow the committed cell to react and behave differently in the same microenvironment.
Keywords: osteoblast progenitors, Runx2, signaling