Reduction of Early Growth Response-1 Gene Expression in Osteoblasts by Hydrogen Peroxide

Bone formation steadily declines with age resulting in a loss of bone mass. Reactive oxygen species (ROS) are thought to be major contributors to the aging process. The zinc finger transcription factor, Early Growth Response-1 (Egr-1) is a potential regulator as a transcription factor of many target genes, and plays a role in cell growth, development, and differentiation. However, the effect of ageing on Egr-1 gene expression has not yet been ascertained. To identify which genes have an altered transcription level associated with bone loss by ageing, the pre-osteoblastic cell MC3T3-E1 was treated with H ₂O₂, and gene expression profiles analyzed with gene chip technology using the Affymetrix GeneChip analysis system (Mouse; 34,000 genes). The expression of many genes in MC3T3-E1 was altered significantly with Egr-1 being decreased by H₂O₂. The reduction of Egr-1 mRNA levels was successfully confirmed by reversed transcription polymerase chain reaction (RT-PCR) and real-time PCR. Since it has been reported that Egr-1 plays an important role as a transcription factor for growth factor genes which promote cell proliferation and differentiation of preosteoblastic cells, the reduction of Egr-1 gene expression by H₂O₂ may be involved in the decline of bone formation in the ageing process.