Novel osteogenic specific transcription factors on mesenchymal stem cells

Objectives:The aim of this study was to find actual transcription factors that are involved in osteogenesis of human mesenchymal stem cells (MSC). Recently, transplantation of MSC has been used as a forceful tool for various regenerative medicines, especially alveolar ridge augmentation in dental field. However, the mechanism of osteogenic differentiation of MSC has not yet fully understood. So in this study, we have investigated wide range of genes those upregulated during osteogenetic differentiation. Methods:Last year we have reported nine transcription factors those might be involved in MSC osteogenesis. After this study, we have added other RNA collected from different condition and tried to find transcription factors those might be related to MSC osteogenesis specifically. New genes were selected by GeneChip (Affimetrix) analysis matched with four categories. Then, those genes were further selected by Ingenuity Pathway Analysis, Database for annotation, Visualization and Integrated Discovery. Small interfering RNAs (siRNA) for these genes were designed and were transfected transiently. The influence of the siRNAs on proliferation and osteogenesis (alkaline phosphatase mRNA levels, alkaline phosphatase activity, alizarin red staining, and calcium content) to MSC were analyzed. Results:Twelve transcription factors those specifically induced at early stage of osteogenic differentiation were identified. However, one transcription factor (GLI2) has previously reported concerning with osteogenic differentiation. So, eleven siRNAs were transfected to MSC and further analyzed. Several transcription factors suppressed MSC proliferation; oppositely some induced and some suppressed osteogenic differentiation of MSC. Conclusions:We have identified eleven novel transcription factors that involves in human MSC osteogenesis. Interaction of these factors might progress MSC osteogenic differentiation. Especially, factors which suppress osteogenic differentiation might show negative feedback toward osteogenic differentiation. Clinical application of these transcription factors might be used for prognostic marker for osteogenic potential of MSC and may be useful for quality check before MSC transplantation.