(-)-Epicatechin Gallate ( ECG) Stimulates Osteoblast Differentiation via Runt- related Transcription Factor 2 ( RUNX2) and Transcriptional Coactivator with PDZ- binding Motif ( TAZ)-mediated Transcriptional Activation*

Abstract

Background: Catechins in green tea have a beneficial effect in bone formation, but the detailed mechanism is not fully understood. Results: ECG, a major compound of green tea, stimulates TAZ- and RUNX2-mediated osteogenic gene transcription through PP1A. Conclusion: ECG stimulates osteoblast differentiation through a transcriptional activation. Significance: A novel mechanism for green tea-stimulated osteoblast differentiation is revealed. Osteoporosis is a degenerative bone disease characterized by low bone mass and is caused by an imbalance between osteoblastic bone formation and osteoclastic bone resorption. It is known that the bioactive compounds present in green tea increase osteogenic activity and decrease the risk of fracture by improving bone mineral density. However, the detailed mechanism underlying these beneficial effects has yet to be elucidated. In this study, we investigated the osteogenic effect of (-)-epicatechin gallate (ECG), a major bioactive compound found in green tea. We found that ECG effectively stimulates osteoblast differentiation, indicated by the increased expression of osteoblastic marker genes. Up-regulation of osteoblast marker genes is mediated by increased expression and interaction of the transcriptional coactivator with PDZ-binding motif (TAZ) and Runt-related transcription factor 2 (RUNX2). ECG facilitates nuclear localization of TAZ through PP1A. PP1A is essential for osteoblast differentiation because inhibition of PP1A activity was shown to suppress ECG-mediated osteogenic differentiation. Taken together, the results showed that ECG stimulates osteoblast differentiation through the activation of TAZ and RUNX2, revealing a novel mechanism for green tea-stimulated osteoblast differentiation.