未找到相关数据
The disease modifying osteoarthritis drug diacerein is able to antagonize pro inflammatory state of chondrocytes under mild mechanical stimuli
被引：26
|作者：
Steinecker-Frohnwieser, B.
[1
]
Weigl, L.
[2
]
Kullich, W.
[1
]
Lohberger, B.
[3
]
机构：
[1] Ludwig Boltzmann Cluster Rheumatol Balneol & Reha, Ludwig Boltzmann Inst Rehabil Internal Dis, Saalfelden, Austria
[2] Med Univ Vienna, Dept Special Anaesthesia & Pain Therapy, Vienna, Austria
[3] Med Univ Graz, Dept Orthopaed Surgety, Graz, Austria
关键词：
Chondrocytes;
Diacerein;
Mechanical stimulation;
Extracellular matrix;
MMP-1;
activity;
qPCR;
NF-KAPPA-B;
ARTICULAR CHONDROCYTES;
CARTILAGE DEGRADATION;
KNEE OSTEOARTHRITIS;
IN-VITRO;
PROLIFERATION;
DIACERHEIN;
EXPRESSION;
RHEIN;
HIP;
D O I：
10.1016/j.joca.2014.05.008
中图分类号：
R826.8 [整形外科学];
R782.2 [口腔颌面部整形外科学];
R726.2 [小儿整形外科学];
R62 [整形外科学（修复外科学）];
学科分类号：
摘要：
Objective: To investigate the combination of mild mechanical stimuli and a disease modifying osteoarthritis drug (DMOAD) in inflammatory activated chondrocytes and to study the combination of drug and mechanical tension on the cellular level as a model for an integrated biophysical approach for osteoarthritis (OA) treatments. Methods: Interleukin-1 beta (IL-1 beta) stimulated C28/I2 cells underwent mild mechanically treatment while cultured in the presence of the DMOAD diacerein. The pharmacological input of diacerein was evaluated by cell viability and cell proliferation measurements. Inflammation and treatment induced changes in key regulatory proteins and components of the extracellular matrix (ECM) were characterized by quantitative real-time PCR (qPCR). The effects on metalloproteinase-1 (MMP-1) activity and glycosaminoglycan (GAG) concentration in cell supernatants of treated cells were investigated. Results: C28/I2 cells demonstrated significant changes in expression of inflammatory and cartilage destructive proteins in response to IL-1 beta stimulation. The chondroprotective action of diacerein in mechanically stimulated cells was mediated by a decrease in interleukin-8 (IL-8), fibronectin-1 (FN-1), collagen type I (Col 1) and MMP-1 expression levels, respectively. Augmented expression of interleukin-6 receptor (IL-6R) and the fibroblast growth factor receptors (FGFRs) by diacerein was not abolished by mechanical treatment. The observed effects were accompanied by a reduced cell proliferation rate, attenuated cell viability and extenuated MMP-1 activity. Conclusion: Diacerein diversely regulates the expression of main regulatory proteins as well as components important to regenerate and set up ECM. Mechanical stimulation does not negatively influence the chondroprotective effect induced by diacerein treatment in immortalized human C28/I2 chondrocytes. (C) 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码：1044 / 1052
页数：9
相关论文