Gene expression profiling in vitamin D sub(3) treated MC3T3-E1 mouse osteoblasts

• Published in: Anticancer research Vol. 28; no. 3A; p. 1620
• Main Authors: Kriebitzsch, C, Verlinden, L, Eelen, G, Beullens, I, Bouillon, R, Verstuyf, A
• Format: Journal Article
• Language: English
• Published: 01.06.2008
• ISSN: 0250-7005

1Alpha,25-dihydroxyvitamin D sub(3) [1 alpha ,25(OH) sub(2)D sub(3)], the active form of vitamin D sub(3), is the ligand of the vitamin D receptor (VDR), which acts as a transcription factor that binds to vitamin D responsive elements (VDRE) in promoter regions of 1 alpha ,25(OH) sub(2)D sub(3)-dependent genes. 1 alpha ,25(OH) sub(2)D sub(3) is an important regulator of serum calcium and phosphorus levels as well as of skeleton homeostasis. Moreover, 1 alpha ,25(OH) sub(2)D sub(3) has potent antiproliferative and prodifferentiative actions on a wide variety of cells, leading to an accumulation of cells in the G1 phase of the cell cycle. The mechanisms responsible for these non-classical effects remain largely unknown and are still under investigation. Therefore, a microarray was performed in MC3T3-E1 mouse osteoblasts, a classical target of 1 alpha ,25(OH) sub(2)D sub(3). Cells were harvested at different time points (6, 12, 24, 36, and 48h) after treatment with vehicle (EtOH) or 10-8M 1 alpha ,25(OH) sub(2)D sub(3). An in-house generated array with approximately 20,000 spotted genes was used. Statistical analysis of the microarray data revealed 15 significant gene clusters. Each cluster was made up of genes that were similarly regulated by 1 alpha ,25(OH) sub(2)D sub(3) during time. One of these gene clusters contained genes that were quickly down-regulated after treatment with 1 alpha ,25(OH) sub(2)D sub(3). A large number of the genes within this cluster are involved in cell cycle regulation. They do not only encode for genes involved in DNA replication but also for proteins that fulfill functions at later stages of the cell cycle (G2 and M phase). Another cluster consisted of genes that were rapidly and strongly induced by 1 alpha ,25(OH) sub(2)D sub(3). The objective of the current study is to focus on both clusters to gain more insights in the mechanism of action of 1 alpha ,25(OH) sub(2)D sub(3).