Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage

Abigail L Clutterbuck; David Allaway; Pat Harris; Ali Mobasheri

doi:10.12688/f1000research.2-147.v2

Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage

F1000Res. 2013 Jul 4:2:147. doi: 10.12688/f1000research.2-147.v2. eCollection 2013.

Authors

Abigail L Clutterbuck¹, David Allaway², Pat Harris², Ali Mobasheri³

Affiliations

¹ School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, LE12 5RD, UK.
² WALTHAM Centre for Pet Nutrition, Waltham-on-the-Wolds, Melton Mowbray, LE14 4RT, UK.
³ 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.

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).

Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

Grants and funding

This work received major financial support from the Biotechnology and Biological Sciences Research Council through the Industrial CASE Studentship programme (Grant Number: BBS/S/M/2006/13141) and minor financial support from the WALTHAM Centre for Pet Nutrition. The BBSRC had no involvement in the study design, data collection, analysis and interpretation. The decision to submit the paper for publication was not influenced by the funding bodies.