title: The disease modifying osteoarthritis drug diacerein is able to antagonize pro inflammatory state of chondrocytes under mild mechanical stimuli.
abstract: 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-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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ludwig Boltzmann Institute for Rehabilitation of Internal Diseases, Ludwig Boltzmann Cluster for Rheumatology, Balneology and Rehabilitation, Saalfelden, Austria. Electronic address: lbi.groebming@aon.at.
authors.forename: B
authors.initials: B
authors.lastname: Steinecker-Frohnwieser
authors.affiliation: Department of Special Anaesthesia and Pain Therapy, Medical University Vienna, Austria.
authors.forename: L
authors.initials: L
authors.lastname: Weigl
authors.affiliation: Ludwig Boltzmann Institute for Rehabilitation of Internal Diseases, Ludwig Boltzmann Cluster for Rheumatology, Balneology and Rehabilitation, Saalfelden, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Kullich
authors.affiliation: Department of Orthopaedic Surgery, Medical University of Graz, Graz, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Lohberger
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D024042:Collagen Type I / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010812:Physical Stimulation; D013314:Stress, Mechanical
chemical_list: D000880:Anthraquinones; D018501:Antirheumatic Agents; D024042:Collagen Type I; C067625:FN1 protein, human; D005353:Fibronectins; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D016209:Interleukin-8; C025292:diacerein; D020781:Matrix Metalloproteinase 1
keywords: Chondrocytes; Diacerein; Extracellular matrix; MMP-1 activity; Mechanical stimulation; qPCR