Journal
OSTEOARTHRITIS AND CARTILAGE
Volume 22, Issue 7, Pages 1044-1052Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2014.05.008
Keywords
Chondrocytes; Diacerein; Mechanical stimulation; Extracellular matrix; MMP-1 activity; qPCR
Categories
Funding
- Ludwig Boltzmann Gesellschaft
- Austrian Pension Insurance Company
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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.
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