Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Steinecker-Frohnwieser, B; Weigl, L; Kullich, W; Lohberger, B.
The disease modifying osteoarthritis drug diacerein is able to antagonize pro inflammatory state of chondrocytes under mild mechanical stimuli.
Osteoarthritis Cartilage. 2014; 22(7):1044-1052
Doi: 10.1016/j.joca.2014.05.008
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Steinecker-Frohnwieser Bibiane
- Co-Autor*innen der Med Uni Graz
- Lohberger Birgit
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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. Interleukin-1beta (IL-1β) 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. C28/I2 cells demonstrated significant changes in expression of inflammatory and cartilage destructive proteins in response to IL-1β 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. 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. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Anthraquinones - pharmacology
- Antirheumatic Agents - pharmacology
- Cell Line -
- Cell Proliferation - drug effects
- Cell Survival - drug effects
- Cells, Cultured -
- Chondrocytes - drug effects
- Chondrocytes - metabolism
- Chondrocytes - pathology
- Collagen Type I - metabolism
- Fibronectins - metabolism
- Glycosaminoglycans - metabolism
- Humans -
- Inflammation - metabolism
- Inflammation - pathology
- Inflammation - prevention & control
- Interleukin-1beta - pharmacology
- Interleukin-8 - metabolism
- Matrix Metalloproteinase 1 - metabolism
- Osteoarthritis - metabolism
- Osteoarthritis - pathology
- Osteoarthritis - prevention & control
- Physical Stimulation -
- Stress, Mechanical -
- Find related publications in this database (Keywords)
- Chondrocytes
- Diacerein
- Mechanical stimulation
- Extracellular matrix
- MMP-1 activity
- qPCR