title: Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage.
abstract: OBJECTIVE
  Curcumin (diferuloylmethane) is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA). The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β)-stimulated inflammation and catabolism in an explant model of cartilage inflammation.
  
  
  METHODS
  Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E 2 (PGE 2) and matrix metalloproteinase (MMP)-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG) release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB) assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days.
  
  
  RESULTS
  Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001) after 24 hours. After 48 hours and five days, curcumin (≥25μM) significantly increased cell death ( p<0.001 both time points). In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM) significantly reduced IL-1β-stimulated PG ( p<0.05) and PGE 2 release ( p<0.001) from explants, whilst curcumin (≥12μM) significantly reduced MMP-3 release ( p<0.01).
  
  
  CONCLUSIONS
  Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.
authors.affiliation: School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, LE12 5RD, UK.
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Clutterbuck
authors.affiliation: WALTHAM Centre for Pet Nutrition, Waltham-on-the-Wolds, Melton Mowbray, LE14 4RT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Allaway
authors.affiliation: WALTHAM Centre for Pet Nutrition, Waltham-on-the-Wolds, Melton Mowbray, LE14 4RT, UK.
authors.forename: Pat
authors.initials: P
authors.lastname: Harris
authors.affiliation: School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, LE12 5RD, UK ; Medical Research Council-Arthritis Research UK Centre for Musculoskeletal Ageing Research, The University of Nottingham, Nottingham, NG7 2UH, UK ; Arthritis Research UK Pain Centre, The University of Nottingham, Nottingham, NG7 2UH, UK ; Arthritis Research UK Centre for Sport, Exercise, and Osteoarthritis, The University of Nottingham, Nottingham, NG7 2UH, UK ; Faculty of Medicine and Health Sciences, The University of Nottingham, Sutton Bonington Campus, LE12 5RD, UK ; School of Pharmacy and Life Sciences, University of Bradford, Bradford, BD7 1DP, UK ; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, 21589, Saudi Arabia ; The D-BOARD European Consortium for Biomarker Discovery, The University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Mobasheri