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

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2014 Feb 12

PMID 24515112

Citations 27

Authors

Mi Ran Byun

Mi Kyung Sung

A Rum Kim

Cham Han Lee

Eun Jung Jang

Mi Gyeong Jeong

Minsoo Noh

Eun Sook Hwang

Jeong-Ho Hong

Affiliations

Soon will be listed here.

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.

Citing Articles

Mechanistic Exploration of Roxb. in Osteoarthritis: Insights from Network Pharmacology, Molecular Docking, and In Vitro Validation.

Ilyas S, Baek C, Manan A, Choi Y, Jo H, Lee D Pharmaceuticals (Basel). 2024; 17(10).

PMID: 39458926 PMC: 11510151. DOI: 10.3390/ph17101285.

The potential application of fermented tea as a drink for regulating bone mass.

Xu Q, Yu Y, Chen K Front Pharmacol. 2024; 15:1353811.

PMID: 39027330 PMC: 11254645. DOI: 10.3389/fphar.2024.1353811.

Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.

Zhu S, Chen W, Masson A, Li Y Cell Discov. 2024; 10(1):71.

PMID: 38956429 PMC: 11219878. DOI: 10.1038/s41421-024-00689-6.

Potential mechanism of tea for treating osteoporosis, osteoarthritis, and rheumatoid arthritis.

Xie X, Fu J, Gou W, Qin Y, Wang D, Huang Z Front Med (Lausanne). 2024; 11:1289777.

PMID: 38420363 PMC: 10899483. DOI: 10.3389/fmed.2024.1289777.

Epicatechin gallate promotes vascularization in co-culture of human osteoblasts and outgrowth endothelial cells.

Zhang L, Wang M, Qiu H, Wei Y, Zhou L, Nian N Exp Biol Med (Maywood). 2023; 248(8):732-745.

PMID: 37354086 PMC: 10408553. DOI: 10.1177/15353702231171894.

References

Varelas X, Sakuma R, Samavarchi-Tehrani P, Peerani R, Rao B, Dembowy J . TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal. Nat Cell Biol. 2008; 10(7):837-48. DOI: 10.1038/ncb1748. View

Lee J, Jin H, Shim H, Kim H, Ha H, Lee Z . Epigallocatechin-3-gallate inhibits osteoclastogenesis by down-regulating c-Fos expression and suppressing the nuclear factor-kappaB signal. Mol Pharmacol. 2009; 77(1):17-25. DOI: 10.1124/mol.109.057877. View

Yang C, Landau J . Effects of tea consumption on nutrition and health. J Nutr. 2000; 130(10):2409-12. DOI: 10.1093/jn/130.10.2409. View

Byun M, Jeong H, Bae S, Kim A, Hwang E, Hong J . TAZ is required for the osteogenic and anti-adipogenic activities of kaempferol. Bone. 2011; 50(1):364-72. DOI: 10.1016/j.bone.2011.10.035. View

Murakami M, Tominaga J, Makita R, Uchijima Y, Kurihara Y, Nakagawa O . Transcriptional activity of Pax3 is co-activated by TAZ. Biochem Biophys Res Commun. 2005; 339(2):533-9. DOI: 10.1016/j.bbrc.2005.10.214. View

Greenblatt M, Shim J, Glimcher L . Mitogen-activated protein kinase pathways in osteoblasts. Annu Rev Cell Dev Biol. 2013; 29:63-79. DOI: 10.1146/annurev-cellbio-101512-122347. View

Shenolikar S, Nairn A . Protein phosphatases: recent progress. Adv Second Messenger Phosphoprotein Res. 1991; 23:1-121. View

Acampora D, Merlo G, Paleari L, Zerega B, Postiglione M, Mantero S . Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5. Development. 1999; 126(17):3795-809. DOI: 10.1242/dev.126.17.3795. View

Lei Q, Zhang H, Zhao B, Zha Z, Bai F, Pei X . TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway. Mol Cell Biol. 2008; 28(7):2426-36. PMC: 2268418. DOI: 10.1128/MCB.01874-07. View

10.

Komori T . Regulation of skeletal development by the Runx family of transcription factors. J Cell Biochem. 2005; 95(3):445-53. DOI: 10.1002/jcb.20420. View

11.

Samee N, Geoffroy V, Marty C, Schiltz C, Vieux-Rochas M, Levi G . Dlx5, a positive regulator of osteoblastogenesis, is essential for osteoblast-osteoclast coupling. Am J Pathol. 2008; 173(3):773-80. PMC: 2527089. DOI: 10.2353/ajpath.2008.080243. View

12.

Nakashima K, de Crombrugghe B . Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet. 2003; 19(8):458-66. DOI: 10.1016/S0168-9525(03)00176-8. View

13.

Mahoney Jr W, Hong J, Yaffe M, Farrance I . The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members. Biochem J. 2005; 388(Pt 1):217-25. PMC: 1186710. DOI: 10.1042/BJ20041434. View

14.

Ducy P, Zhang R, Geoffroy V, Ridall A, Karsenty G . Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997; 89(5):747-54. DOI: 10.1016/s0092-8674(00)80257-3. View

15.

Chan S, Lim C, Shen Loo L, Chong Y, Huang C, Hong W . TEADs mediate nuclear retention of TAZ to promote oncogenic transformation. J Biol Chem. 2009; 284(21):14347-58. PMC: 2682883. DOI: 10.1074/jbc.M901568200. View

16.

Hong J, Hwang E, McManus M, Amsterdam A, Tian Y, Kalmukova R . TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science. 2005; 309(5737):1074-8. DOI: 10.1126/science.1110955. View

17.

Park K, Whitsett J, Di Palma T, Hong J, Yaffe M, Zannini M . TAZ interacts with TTF-1 and regulates expression of surfactant protein-C. J Biol Chem. 2004; 279(17):17384-90. DOI: 10.1074/jbc.M312569200. View

18.

Barry E, Camargo F . The Hippo superhighway: signaling crossroads converging on the Hippo/Yap pathway in stem cells and development. Curr Opin Cell Biol. 2013; 25(2):247-53. DOI: 10.1016/j.ceb.2012.12.006. View

19.

Zhang H, Liu C, Zha Z, Zhao B, Yao J, Zhao S . TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J Biol Chem. 2009; 284(20):13355-13362. PMC: 2679435. DOI: 10.1074/jbc.M900843200. View

20.

Murakami M, Nakagawa M, Olson E, Nakagawa O . A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome. Proc Natl Acad Sci U S A. 2005; 102(50):18034-9. PMC: 1312418. DOI: 10.1073/pnas.0509109102. View