Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis

Abstract

Osteoarthritis and rheumatoid arthritis are characterized by focal loss of cartilage due to an up-regulation of catabolic pathways, induced mainly by pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha). Since reactive oxygen species are also involved in this extracellular-matrix-degrading activity, we aimed to compare the chondrocyte oxidative status responsible for cartilage damage occurring in primarily degenerative (osteoarthritis) and inflammatory (rheumatoid arthritis) joint diseases. Human articular chondrocytes were isolated from patients with osteoarthritis or rheumatoid arthritis, or from multi-organ donors, and stimulated with IL-1beta and/or TNFalpha. We evaluated the oxidative stress related to reactive nitrogen and oxygen intermediates, measuring NO(-)(2) as a stable end-product of nitric oxide generation and superoxide dismutase as an antioxidant enzyme induced by radical oxygen species. We found that cells from patients with osteoarthritis produced higher levels of NO(-)(2) than those from patients with rheumatoid arthritis. In addition, IL-1beta was more potent than TNFalpha in inducing nitric oxide in both arthritides, and TNFalpha alone was almost ineffective in cells from rheumatoid arthritis patients. We also observed that the intracellular content of copper/zinc superoxide dismutase (Cu/ZnSOD) was always lower in rheumatoid arthritis chondrocytes than in those from multi-organ donors, whereas no differences were found in intracellular manganese SOD (MnSOD) or in supernatant Cu/ZnSOD and MnSOD levels. Moreover, intracellular MnSOD was up-regulated by cytokines in osteoarthritis chondrocytes. In conclusion, our results suggest that nitric oxide may play a major role in altering chondrocyte functions in osteoarthritis, whereas the harmful effects of radical oxygen species are more evident in chondrocytes from patients with rheumatoid arthritis, due to an oxidant/antioxidant imbalance.

RAP-PCR fingerprinting reveals time-dependent expression of matrix-related molecules following stem-cell based TGFβ1-induced chondrocyte development

“…We found elevated MnSOD mRNA expression in chondrocytes after TGF-β1 induction. This findings is in line with results from Mazzetti et al who reported up-regulation of intracellular MnSOd in osteoarthritic chondrocytes in response to several cytokines; this up-regulation was interpreted as a compensatory reaction to the higher nitric oxide levels in osteoarthritis chondrocytes compared to rheumatoid arthritis chondrocytes (29). Moreover, superoxide dismutase has been shown to effectively prevent interleukin-1β IκBα degradation and, thus, inhibit inducible nitric oxide synthase (iNOS) expression (30), as well as production of ROS induced by tensile stress (31).…”

Estradiol protects cultured articular chondrocytes from oxygen-radical-induced damage

“…Several studies have shown that ROS are involved in the degradation of the extracellular matrix of articular cartilage (Mazetti et al 2001) and the suppression of proteoglycan synthesis (Bates et al 1984;Schalwijk et al 1985;Tiku et al 1999). Superoxide radicals, generated enzymatically by the action of xanthine oxidase on hypoxanthine, significantly reduce proteoglycan synthesis of cultured bovine articular cartilage as demonstrated by 35 S-sulphate incorporation (Bates et al 1984).…”

The antioxidant potential of Sutherlandia frutescens

“…Neutrophil derived reactive oxygen intermediates, such as hydrogen peroxide and superoxide radicals, are responsible for the pathogenesis of various inflammatory conditions (Halliwell, 1994;Gafvert et al, 2002;Mazzetti et al, 2001;Hanson and Clegg, 2002;Loukides et al, 2002). The antiinflammatory properties of various medicinal plant extracts have been explained, at least in part, by their antioxidant activities (Gerritsen et al, 1995;Gali-Muhtasib et al, 1999;Schinella et al, 2002;Lindsey et al, 2002).…”