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
[31]   Systemic tumor necrosis factor α mediates an increase in peripheral CD11bhigh osteoclast precursors in tumor necrosis factor α-transgenic mice [J].
Li, P ;
Schwarz, EM ;
O'Keefe, RJ ;
Ma, L ;
Looney, RJ ;
Ritchlin, CT ;
Boyce, BF ;
Xing, LP .
ARTHRITIS AND RHEUMATISM, 2004, 50 (01) :265-276
[32]   Endogenous TNFα lowers maximum peak bone mass and inhibits osteoblastic smad activation through NF-κB [J].
Li, Yan ;
Li, Aimin ;
Strait, Karen ;
Zhang, Hongying ;
Nanes, Mark S. ;
Weitzmann, M. Neale .
JOURNAL OF BONE AND MINERAL RESEARCH, 2007, 22 (05) :646-655
[33]   Transcriptional regulation of the osterix (Osx, Sp7) promoter by tumor necrosis factor identifies disparate effects of mitogen-activated protein kinase and NFκB pathways [J].
Lu, XH ;
Gilbert, L ;
He, XF ;
Rubin, J ;
Nanes, MS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (10) :6297-6306
[34]  
Mukherjee S, 2008, J CLIN INVEST, V118, P491, DOI [10.1172/JC133102, 10.1172/JCI33102]
[35]   Changes in proinflammatory cytokine activity after menopause [J].
Pfeilschifter, J ;
Köditz, R ;
Pfohl, M ;
Schatz, H .
ENDOCRINE REVIEWS, 2002, 23 (01) :90-119
[36]   Pathogenesis of osteoporosis: concepts, conflicts, and prospects [J].
Raisz, LG .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (12) :3318-3325
[37]   IκB kinase (IKK)β, but not IKKα, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss [J].
Ruocco, MG ;
Maeda, S ;
Park, JM ;
Lawrence, T ;
Hsu, LC ;
Cao, YX ;
Schett, G ;
Wagner, EF ;
Karin, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (10) :1677-1687
[38]   IkB kinase-α acts in the epidermis to control skeletal and craniofacial morphogenesis [J].
Sil, AK ;
Maeda, S ;
Sano, Y ;
Roop, DR ;
Karin, M .
NATURE, 2004, 428 (6983) :660-664
[39]   NF-κB functions-in osteoclasts [J].
Soysa, N. S. ;
Alles, N. .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 378 (01) :1-5
[40]   Limb and skin abnormalities in mice lacking IKKα [J].
Takeda, K ;
Takeuchi, O ;
Tsujimura, T ;
Itami, S ;
Adachi, O ;
Kawai, T ;
Sanjo, H ;
Yoshikawa, K ;
Terada, N ;
Akira, S .
SCIENCE, 1999, 284 (5412) :313-316