Background The medical application of disease modifying osteoarthritis drugs (DMOADs) in OA therapy emerged to preserve normal joint function, to reduce disease's intensity and symptoms and to restrain the progression rate of OA1. The DMOAD diacerein reduces the severity of OA and may be able to modify the course of the disease2 by down regulating the interleukin-1β (IL-1β) induced inflammatory pathways. Alternatively, dynamic loading of joints as a non-drug treatment modality in OA patients has demonstrated its effectiveness on the reduction of pain and improvement of function3,4. In vitro studies implicated a direct mechano-sensitive, anti-inflammatory effect in joint tissues exposed to moderate levels of cyclic hydrostatic pressure.
Objectives To investigate the combination of mild mechanical stimuli and a DMOAD in inflammatory activated chondrocytes and to study the combination of drug and exercise therapy on the cellular level as a model for an integrated biophysical approach for osteoarthritis (OA) treatments.
Methods Interleukin 1beta stimulated C28/I2 cells underwent mild mechanical treatment while cultured in the presence of 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 were characterized by quantitative real-time PCR (qPCR). In addition, 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 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 (IL6R) and the fibroblast growth factor receptors (FGFR) by diacerein was not abolished by mechanical treatment of the cells. The observed effects were accompanied by a reduced cell proliferation rate, attenuated cell viability and extenuated MMP-1 activity.
Conclusions Diacerein diversely regulates the expression of main regulatory proteins as well as components important to regenerate and set up extracellular matrix. Mechanical stimulation does not negatively influence the chondroprotective effect induced by diacerein treatment in immortalized human C28/I2 chondrocytes.
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Disclosure of Interest None declared
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