Influence of glucosamine sulphate on oxidative stress in human osteoarthritic chondrocytes: effects on HO-1, p22Phox and iNOS expression
1Rheumatology Unit, Department of Clinical and Experimental Medicine, 2Clinica Medica I, Department of Medical and Surgical Sciences and 3Department of Medical and Surgical Specialties, Orthopaedic Clinic, University of Padova, Italy.
Correspondence to: L. Punzi, Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padova, Via Giustiniani, 2-35128 Padova, Italy. E-mail: punzireu{at}unipd.it
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Abstract |
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Objective. Reactive oxygen species (ROS) are major determinants in the alteration of articular cartilage. Among protective cellular mechanisms, the inducible isoform of haem oxygenase (HO-1) plays a particularly relevant role. On the other hand, the enzymatic activity of the Nicotinamide adenine dinucleotide phosphate (NADPH) system could contribute to the generation of ROS. Glucosamine sulphate (GS) is one of the drugs used in the treatment of osteoarthritis; however, its mechanism of action is still largely unknown. The aim of the present study was to investigate the effects of GS on primary human chondrocytes in vitro, in particular with regard to HO-1, p22Phox (a subunit of NADPH complex) and inducible nitric oxide synthase (iNOS) expression.
Methods. Primary human chondrocytes were treated with different concentrations of GS; gene expression of HO-1, p22Phox and iNOS was assessed by the reverse transcriptase–polymerase chain reaction method. In a separate set of experiments, the cells were stimulated with human recombinant interleukin (IL)-1β and simultaneously treated with GS. Moreover, HO-1 protein and total nitrite production were evaluated.
Results. HO-1 gene expression was up-regulated (+40% with respect to the controls, P < 0.001) by 10 mmol/l GS at 24 h, while p22Phox gene expression was down-regulated by 10 mmol/l GS with a maximum inhibitory effect observed after 48 h treatment. IL-1β stimulation induced expression of iNOS reverted by 1 and 10 mmol/l GS. Moreover, HO-1 gene expression was down-regulated by IL-1β and 10 mmol/l GS restored baseline values. These data were confirmed by evaluating HO-1 protein level and nitrite production.
Conclusions. The influence of GS on oxidative stress observed in this study discloses a possible new mechanism of action and seems to be in keeping with a potential protective effect on chondrocyte population.
KEY WORDS: Glucosamine sulphate, Osteoarthritis, Chondrocytes, Haemoxygenase, p22Phox
Submitted 15 January 2007;
revised version accepted 20 July 2007.
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