Novel functions for NFκB: inhibition of bone formation

被引:139
作者
Krum, Susan A. [2 ]
Chang, Jia [1 ]
Miranda-Carboni, Gustavo [3 ]
Wang, Cun-Yu [1 ]
机构
[1] UCLA Sch Dent, Div Oral Biol & Med, Lab Mol Signaling, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthopaed Surg, UCLA Orthopaed Hosp, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA
关键词
TUMOR-NECROSIS-FACTOR; OSTEOCLAST DIFFERENTIATION; ESTROGEN DEFICIENCY; RECEPTOR ACTIVATOR; TRANSGENIC MICE; FACTOR-ALPHA; TNF-ALPHA; IKK-ALPHA; IN-VIVO; OSTEOPOROSIS;
D O I
10.1038/nrrheum.2010.133
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
NF kappa B is a family of transcription factors involved in immunity and the normal functioning of many tissues. It has been well studied in osteoclasts, and new data indicate an important role for NF kappa B in the negative regulation of bone formation. In this article, we discuss how NF kappa B activation affects osteoblast function and bone formation. In particular, we describe how reduced NF kappa B activity in osteoblasts results in an increase in bone formation via enhanced c-Jun N-terminal kinase (JNK) activity, which regulates FOSL1 (also known as Fra1) expression. Furthermore, we discuss how estrogen and NF kappa B crosstalk in osteoblasts acts to oppositely regulate bone formation. Future NF kappa B-targeting treatments for osteoporosis, rheumatoid arthritis and other inflammatory bone diseases could lead to increased bone formation concurrent with decreased bone resorption.
引用
收藏
页码:607 / 611
页数:5
相关论文
共 48 条
[1]   Osteoclast differentiation and activation [J].
Boyle, WJ ;
Simonet, WS ;
Lacey, DL .
NATURE, 2003, 423 (6937) :337-342
[2]   Inhibition of osteoblastic bone formation by nuclear factor-κB [J].
Chang, Jia ;
Wang, Zhuo ;
Tang, Eric ;
Fan, Zhipeng ;
McCauley, Laurie ;
Franceschi, Renny ;
Guan, Kunliang ;
Krebsbach, Paul H. ;
Wang, Cun-Yu .
NATURE MEDICINE, 2009, 15 (06) :682-U120
[3]   Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor κB-independent bone morphogenetic protein/Smad signaling [J].
Chen, SQ ;
Guttridge, DC ;
Tang, E ;
Shi, ST ;
Guan, KL ;
Wang, CY .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (42) :39259-39263
[4]   Ubiquitin signalling in the NF-κB pathway [J].
Chen, ZJJ .
NATURE CELL BIOLOGY, 2005, 7 (08) :758-U19
[5]   Distinct roles of unliganded and liganded estrogen receptors in transcriptional repression [J].
Cvoro, A ;
Tzagarakis-Foster, C ;
Tatomer, D ;
Paruthiyil, S ;
Fox, MS ;
Leitman, DC .
MOLECULAR CELL, 2006, 21 (04) :555-564
[6]   Induction of gadd45β by NF-κB downregulates pro-apoptotic JNK signalling [J].
De Smaele, E ;
Zazzeroni, F ;
Papa, S ;
Nguyen, DU ;
Jin, RG ;
Jones, J ;
Cong, R ;
Franzoso, G .
NATURE, 2001, 414 (6861) :308-313
[7]   Future therapeutic targets in osteoporosis [J].
Deal, Chad .
CURRENT OPINION IN RHEUMATOLOGY, 2009, 21 (04) :380-385
[8]   TNF-α and IL-1β inhibit RUNX2 and collagen expression but increase alkaline phosphatase activity and mineralization in human mesenchymal stem cells [J].
Ding, J. ;
Ghali, O. ;
Lencel, P. ;
Broux, O. ;
Chauveau, C. ;
Devedjian, J. C. ;
Hardouin, P. ;
Magne, D. .
LIFE SCIENCES, 2009, 84 (15-16) :499-504
[9]   The Fos-related antigen Fra-1 is an activator of bone matrix formation [J].
Eferl, R ;
Hoebertz, A ;
Schilling, AF ;
Rath, M ;
Karreth, F ;
Kenner, L ;
Amling, M ;
Wagner, EF .
EMBO JOURNAL, 2004, 23 (14) :2789-2799
[10]   Requirement for NF-κB in osteoclast and B-cell development [J].
Franzoso, G ;
Carlson, L ;
Xing, LP ;
Poljak, L ;
Shores, EW ;
Brown, KD ;
Leonardi, A ;
Tran, T ;
Boyce, BF ;
Siebenlist, U .
GENES & DEVELOPMENT, 1997, 11 (24) :3482-3496