title: (-)-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: 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.
authors: From the Division of Life Sciences, Korea University, Seoul 136-701, Korea.
authors: Mi Ran
authors: MR
authors: Byun
authors: Mi Kyung
authors: MK
authors: Sung
authors: A Rum
authors: AR
authors: Kim
authors: Cham Han
authors: CH
authors: Lee
authors: Eun Jung
authors: EJ
authors: Jang
authors: Mi Gyeong
authors: MG
authors: Jeong
authors: Minsoo
authors: M
authors: Noh
authors: Eun Sook
authors: ES
authors: Hwang
authors: Jeong-Ho
authors: JH
authors: Hong
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000217:Acyltransferases; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; C493716:Runx2 protein, mouse; D014157:Transcription Factors; D002392:Catechin; C062669:epicatechin gallate; D000217:Acyltransferases; C486363:tafazzin protein, mouse; C108675:TAFAZZIN protein, human; D054648:Protein Phosphatase 2
keywords: Cell Differentiation; Mesenchymal Stem Cells; Molecular Cell Biology; Osteoblasts; Pharmacology