Overexpression of HMGB1 A-box reduced IL-1β-induced MMP expression and the production of inflammatory mediators in human chondrocytes

被引：60
作者：
Fu, Yahui [1 ]
Lei, Jinlai [1 ]
Zhuang, Yan [1 ]
Zhang, Kun [1 ]
Lu, Daigang [1 ]
机构：
[1] Xi An Jiao Tong Univ, Hlth Sci Ctr, Dept Orthopaed Trauma, Xian Honghui Hosp, Xian 710054, Peoples R China
来源：
EXPERIMENTAL CELL RESEARCH | 2016年 / 349卷 / 01期
关键词：
High mobility group box 1 A-box (HMGB1 A-box); Matrix metalloproteinase (MMP); Toll-like receptor 4 (TRL4); Nuclear factor-kappa B (NF-kappa B); Osteoarthritis (OA); NITRIC-OXIDE; GENE-EXPRESSION; ARTICULAR CHONDROCYTES; KAPPA-B; CARTILAGE; INHIBITORS; METALLOPROTEINASES;
D O I：
10.1016/j.yexcr.2016.10.014
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) plays a crucial role in the pathogenesis of osteoarthritis (OA) by stimulating several mediators that contribute to cartilage degradation. The aim of this study was to investigate the effects and mechanism of high mobility group box 1 (HMGB1) inhibitors HMGB1 A-box on the expression of matrix metalloproteinase (MMP) and the production of inflammatory mediators in human osteoarthritis chondrocytes after activation by IL-1 beta. We found that the overexpression of HMGB1 A box significantly decreased the IL-1 beta-stimulated the production of MMP-1, MMP-3 and MMP-9, and also reduced the elevated levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) associated with the inhibition of prostaglandin E2 (PGE2) and nitric oxide (NO) production in IL-1 beta-stimulated chondrocytes. In addition, overexpression of the HMGB1 A-box significantly inhibited the up-regulation of ADAMTS-4, ADAMTS-5 and HMGBI caused by IL-1 beta in chondrocytes. Moreover, the overexpression of HMGB1 A-box markedly suppressed the IL-1 beta-mediated activation of the Toll-like receptor 4 (TRL4)/NF-kappa B pathway. Our observations indicated that the HMGB1 A-box can play a protective role by suppressing the IL-1 beta-induced expression of MMPs and that the production of inflammatory mediators in chondrocytes was associated with suppression of the HMGB1/TLR4/NF-kappa B pathway. In conclusion, HMGB1 A-box relieves the development of OA that may be associated with regulating the HMGB1/TLR4/NF-kappa B pathway.
引用
收藏
页码：184 / 190
页数：7
相关论文
共 28 条
[1]  
Andersson U, 2002, J LEUKOCYTE BIOL, V72, P1084
[2]   High-mobility group box-1 in ischemia-reperfusion injury of the heart [J].
Andrassy, Martin ;
Volz, Hans C. ;
Igwe, John C. ;
Funke, Benjamin ;
Eichberger, Sebastian N. ;
Kaya, Ziya ;
Buss, Sebastian ;
Autschbach, Frank ;
Pleger, Sven T. ;
Lukic, Ivan K. ;
Bea, Florian ;
Hardt, Stefan E. ;
Humpert, Per M. ;
Bianchi, Marco E. ;
Mairbaeurl, Heimo ;
Nawroth, Peter P. ;
Remppis, Andrew ;
Katus, Hugo A. ;
Bierhaus, Angelika .
CIRCULATION, 2008, 117 (25) :3216-3226
[3]   Avocado soybean unsaponifiables (ASU) suppress TNF-α, IL-1β, COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages [J].
Au, R. Y. ;
Al-Talib, T. K. ;
Au, A. Y. ;
Phan, P. V. ;
Frondoza, C. G. .
OSTEOARTHRITIS AND CARTILAGE, 2007, 15 (11) :1249-1255
[4]   Histone deacetylase inhibitors suppress interleukin-1β-induced nitric oxide and prostaglandin E2 production in human chondrocytes [J].
Chabane, N. ;
Zayed, N. ;
Afif, H. ;
Mfuna-Endam, L. ;
Benderdour, M. ;
Boileau, C. ;
Martel-Pelletier, J. ;
Pelletier, J. -P. ;
Duval, N. ;
Fahmi, H. .
OSTEOARTHRITIS AND CARTILAGE, 2008, 16 (10) :1267-1274
[5]   Honokiol, A Low Molecular Weight Natural Product, Prevents Inflammatory Response and Cartilage Matrix Degradation in Human Osteoarthritis Chondrocytes [J].
Chen, Ying Ju ;
Tsai, Keh Sung ;
Chan, Ding Cheng ;
Lan, Kuo Cheng ;
Chen, Cheng Feng ;
Yang, Rong Sen ;
Liu, Shing Hwa .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2014, 32 (04) :573-580
[6]   The Interleukin 1β Pathway in the Pathogenesis of Osteoarthritis [J].
Daheshia, Massoud ;
Yao, Jian Q. .
JOURNAL OF RHEUMATOLOGY, 2008, 35 (12) :2306-2312
[7]   Cyclooxygenase inhibitors - current status and future prospects [J].
Dannhardt, G ;
Kiefer, W .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2001, 36 (02) :109-126
[8]  
Fernandes JC, 2002, BIORHEOLOGY, V39, P237
[9]   AKIP1 enhances NF-κB-dependent gene expression by promoting the nuclear retention and phosphorylation of p65 [J].
Gao, Nan ;
Asamitsu, Kaori ;
Hibi, Yurina ;
Ueno, Takaharu ;
Okamoto, Takashi .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (12) :7834-7843
[10]   Cartilage homeostasis in health and rheumatic diseases [J].
Goldring, Mary B. ;
Marcu, Kenneth B. .
ARTHRITIS RESEARCH & THERAPY, 2009, 11 (03)
123