|発表タイトル||Statin Regulates Runx2 Expression in Human Dental Pulp Stem Cells.|
|学会名||91st General Session & Exhibition of the IADR|
|発表者・共同発表者||Kamada A, Ikeo T, Tamura I, Goda S, Yoshikawa Y, Domae E, Yoshimoto H, Kakudo K|
|開催地||Seattle, WA, USA|
|概要||Objective: Statins, the cholesterol-lowering drug, are known to activate the promoter of the bone morphogenic protein-2 (BMP-2) gene, and stimulate bone formation. Previously, we demonstrated that statins directly suppressed the over-expression of runt-related transcription factor 2 (Runx2) mRNA in the human osteoblastic osteosarcoma cells. Runx2 is thought to determine the osteoblast lineage from pluripotent mesenchymal cells, enhance osteoblast differentiation at an early stage, and inhibit osteoblast differentiation at a late stage. Recently statin has also reported to promote the odontogenic differentiation of dental pulp stem cells. In this study, we examine the effect of statin on the Runx2 gene expression in dental pulp stem cells.
Method: Dental pulp cell cultures from impacted third molars were established and maintained in standard medium. Odontogenic differentiation was induced by differential medium including ascorbic acid and β-glycerophosphate with simvastatin or mevastatin, and gene expression level was measured using real-time quantitative RT-PCR technique.
Result: In the early stages, statin promoted the gene expressions of BMP-2, Runx2 and dentin sialophosphoprotein (DSPP) in the dental pulp cells. Subsequently, the relative levels of mRNA expression for osteocalcin increased significantly in the statin stimulated cells, and Runx2 gene expression was suppressed with the progress of calcification. The mineralized matrix produced by the cultured dental pulp cells was visualized by von Kossa staining.
Conclusion: Hence, it is indicated that statins induce not only the initial odontogenic differentiation of human dental pulp stem cells but also final differentiation through the regulation of transcription factors.