Inhibition of Notch1 Signaling by Runx2 During Osteoblast Differentiation

被引:57
作者
Ann, Eun-Jung [1 ]
Kim, Hwa-Young [1 ]
Choi, Yun-Hee [1 ]
Kim, Mi-Yeon [1 ]
Mo, Jung-Soon [1 ]
Jung, Jane [1 ]
Yoon, Ji-Hye [1 ]
Kim, Su-Man [1 ]
Moon, Jeong-Sik [1 ]
Seo, Mi-Sun [1 ]
Hong, Ji-Ae [1 ]
Jang, Won-Gu [4 ]
Shore, Paul [2 ]
Komori, Toshihisa [3 ]
Koh, Jeong-Tae [4 ]
Park, Hee-Sae [1 ]
机构
[1] Chonnam Natl Univ, Sch Biol Sci & Technol, Hormone Res Ctr, Kwangju 500757, South Korea
[2] Univ Manchester, Fac Life Sci, Manchester, Lancs, England
[3] Nagasaki Univ, Grad Sch Biomed Sci, Dept Cell Biol, Unit Basic Med Sci, Nagasaki 852, Japan
[4] Chonnam Natl Univ, Sch Dent, Dept Pharmacol & Dent Therapeut, Kwangju 500757, South Korea
关键词
NOTCH1; RUNX2; OSTEOBLAST DIFFERENTIATION; ENDOTHELIAL-CELLS; MYOD EXPRESSION; GENE-FAMILY; DEGRADATION; GROWTH; TRANSCRIPTION; DROSOPHILA; PATHWAYS; ACTIVATION; KINASE;
D O I
10.1002/jbmr.227
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Notch1 genes encode receptors for a signaling pathway that regulates cell growth and differentiation in various contexts, but the role of Notch1 signaling in osteogenesis is not well defined. Notch1 controls osteoblast differentiation by affecting Runx2, but the question arises whether normal osteoblastic differentiation can occur regardless of the presence of Notch1. In this study, we observed the downregulation of Notch1 signaling during osteoblastic differentiation. BMPR-IB/Alk6-induced Runx2 proteins reduced Notch1 activity to a marked degree. Accumulated Runx2 suppressed Notch1 transcriptional activity by dissociating the Notch1-IC-RBP-Jk complex. Using deletion mutants, we also determined that the N-terminal domain of Runx2 was crucial to the binding and inhibition of the N-terminus of the Notch1 intracellular domain. Notably, upregulation of the Runx2 protein level paralleled reduced expression of Hes1, which is a downstream target of Notch1, during osteoblast differentiation. Collectively, our data suggest that Runx2 is an inhibitor of the Notch1 signaling pathway during normal osteoblast differentiation. (C) 2011 American Society for Bone and Mineral Research.
引用
收藏
页码:317 / 330
页数:14
相关论文
共 52 条
[1]
Genetic interactions among vestigial, hairy, and notch suggest a role of vestigial in the differentiation of epidermal and neural cells of the wing and halter of Drosophila melanogaster [J].
AbuIssa, R ;
Cavicchi, S .
JOURNAL OF NEUROGENETICS, 1996, 10 (04) :239-246
[2]
Anant S, 1998, DEVELOPMENT, V125, P1361
[3]
Notch signaling: Cell fate control and signal integration in development [J].
Artavanis-Tsakonas, S ;
Rand, MD ;
Lake, RJ .
SCIENCE, 1999, 284 (5415) :770-776
[4]
Transcriptional mechanisms regulating MyoD expression in the mouse [J].
Chen, JCJ ;
Goldhamer, DJ .
CELL AND TISSUE RESEARCH, 1999, 296 (01) :213-219
[5]
Runx2 regulates FGF2-induced Bmp2 expression during cranial bone development [J].
Choi, KY ;
Kim, HJ ;
Lee, MH ;
Kwon, TG ;
Nah, HD ;
Furuichi, T ;
Komori, T ;
Nam, SH ;
Kim, YJ ;
Kim, HJ ;
Ryoo, HM .
DEVELOPMENTAL DYNAMICS, 2005, 233 (01) :115-121
[6]
deCelis JF, 1996, DEVELOPMENT, V122, P2719
[7]
Runx2-mediated activation of the Bax gene increases osteosarcoma cell sensitivity to apoptosis [J].
Eliseev, R. A. ;
Dong, Y-F ;
Sampson, E. ;
Zuscik, M. J. ;
Schwarz, E. M. ;
O'Keefe, R. J. ;
Rosier, R. N. ;
Drissi, M. H. .
ONCOGENE, 2008, 27 (25) :3605-3614
[8]
Dimorphic effects of Notch signaling in bone homeostasis [J].
Engin, Feyza ;
Yao, Zhenqiang ;
Yang, Tao ;
Zhou, Guang ;
Bertin, Terry ;
Jiang, Ming Ming ;
Chen, Yuqing ;
Wang, Lisa ;
Zheng, Hui ;
Sutton, Richard E. ;
Boyce, Brendan F. ;
Lee, Brendan .
NATURE MEDICINE, 2008, 14 (03) :299-305
[9]
Notch signaling contributes to the pathogenesis of human osteosarcomas [J].
Engin, Feyza ;
Bertin, Terry ;
Ma, Ou ;
Jiang, Ming Ming ;
Wang, Lisa ;
Sutton, Richard E. ;
Donehower, Lawrence A. ;
Lee, Brendan .
HUMAN MOLECULAR GENETICS, 2009, 18 (08) :1464-1470
[10]
PTH/PTHrP receptor delays chondrocyte hypertrophy via both Runx2-dependent and -independent pathways [J].
Guo, J ;
Chung, UI ;
Yang, DH ;
Karsenty, G ;
Bringhurst, FR ;
Kronenberg, HM .
DEVELOPMENTAL BIOLOGY, 2006, 292 (01) :116-128