Glucocorticoids Antagonize RUNX2 During Osteoblast Differentiation in Cultures of ST2 Pluripotent Mesenchymal Cells

作者: Theodora Koromila , Sanjeev K. Baniwal , Yae S. Song , Anthony Martin , Jian Xiong

DOI: 10.1002/JCB.24646

关键词:

摘要: The efficacy of glucocorticoids (GCs) in treating a wide range autoimmune and inflammatory conditions is blemished by severe side effects, including osteoporosis. chief mechanism leading to GC-induced osteoporosis inhibition bone formation, but the role RUNX2, master regulator osteoblast differentiation has not been well studied. We assessed effects synthetic GC dexamethasone (dex) on transcription RUNX2-stimulated genes during mesenchymal pluripotent cells into osteoblasts. Dex inhibited RUNX2 reporter gene attenuated locus-dependently RUNX2-driven expression several endogenous target genes. anti-RUNX2 activity dex was attributable decreased expression, rather physical interaction between receptor (GR), demonstrated co-immunoprecipitation assays co-immunofluorescence imaging. Investigation RUNX2/GR may lead development bone-sparing treatment modalities for management diseases.

参考文章(28)
S. K. Baniwal, P. K. Shah, Y. Shi, J. H. Haduong, Y. A. DeClerck, Y. Gabet, B. Frenkel, Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2 mesenchymal progenitor cells. Osteoporosis International. ,vol. 23, pp. 1399- 1413 ,(2012) , 10.1007/S00198-011-1728-5
Ernesto Canalis, Effect of cortisol on periosteal and nonperiosteal collagen and DNA synthesis in cultured rat calvariae. Calcified Tissue International. ,vol. 36, pp. 158- 166 ,(1984) , 10.1007/BF02405312
Na Kyung Lee, Hideaki Sowa, Eiichi Hinoi, Mathieu Ferron, Jong Deok Ahn, Cyrille Confavreux, Romain Dacquin, Patrick J. Mee, Marc D. McKee, Dae Young Jung, Zhiyou Zhang, Jason K. Kim, Franck Mauvais-Jarvis, Patricia Ducy, Gerard Karsenty, Endocrine Regulation of Energy Metabolism by the Skeleton Cell. ,vol. 130, pp. 456- 469 ,(2007) , 10.1016/J.CELL.2007.05.047
Thomas L. McCarthy, Wei-Zhong Chang, Yuan Liu, Michael Centrella, Runx2 integrates estrogen activity in osteoblasts. Journal of Biological Chemistry. ,vol. 278, pp. 43121- 43129 ,(2003) , 10.1074/JBC.M306531200
Yang-Min Ning, Diane M. Robins, AML3/CBFα1 Is Required for Androgen-specific Activation of the Enhancer of the Mouse Sex-limited Protein (Slp) Gene Journal of Biological Chemistry. ,vol. 274, pp. 30624- 30630 ,(1999) , 10.1074/JBC.274.43.30624
Patricia Ducy, Rui Zhang, Valérie Geoffroy, Amy L Ridall, Gérard Karsenty, Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation Cell. ,vol. 89, pp. 747- 754 ,(1997) , 10.1016/S0092-8674(00)80257-3
T Komori, H Yagi, S Nomura, A Yamaguchi, K Sasaki, K Deguchi, Y Shimizu, R.T Bronson, Y.-H Gao, M Inada, M Sato, R Okamoto, Y Kitamura, S Yoshiki, T Kishimoto, Targeted Disruption of Cbfa1 Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts Cell. ,vol. 89, pp. 755- 764 ,(1997) , 10.1016/S0092-8674(00)80258-5
Baruch Frenkel, Albert Hong, Sanjeev K. Baniwal, Gerhard A. Coetzee, Claes Ohlsson, Omar Khalid, Yankel Gabet, Regulation of adult bone turnover by sex steroids. Journal of Cellular Physiology. ,vol. 224, pp. 305- 310 ,(2010) , 10.1002/JCP.22159
Ulrike Baschant, Nancy E. Lane, Jan Tuckermann, The multiple facets of glucocorticoid action in rheumatoid arthritis Nature Reviews Rheumatology. ,vol. 8, pp. 645- 655 ,(2012) , 10.1038/NRRHEUM.2012.166
R S Weinstein, R L Jilka, A M Parfitt, S C Manolagas, Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. Journal of Clinical Investigation. ,vol. 102, pp. 274- 282 ,(1998) , 10.1172/JCI2799