Staphylococcus aureus stimulates inducible nitric oxide synthase in articular cartilage

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Abstract
Objective To determine if Staphylococcus aureus stimulates the L-arginine–nitric oxide (NO) synthase pathway in articular cartilage. Methods A heat-killed and sonicated (denatured) S aureus preparation was added to cultures of bovine articular cartilage. NO production was measured as accumulated nitrite in the culture medium and by the NO synthase–dependent conversion of 3H–L-arginine to 3H–L-citrulline in cartilage homogenates. Inducible NO synthase (iNOS) messenger RNA (mRNA) expression was analyzed by Northern blot. Proteoglycan synthesis was measured by 35SO4 incorporation into glycosaminoglycan. Results Nitrite accumulation and 3H–L-citrulline formation in cartilage were elevated by denatured S aureus (compared with unstimulated control cartilage) and inhibited by the NO synthase inhibitor NG-monomethyl-L-arginine. Northern blot analysis revealed increased iNOS mRNA expression in bovine chondrocytes in response to denatured S aureus stimulation. Denatured S aureus suppressed the accumulation of 35SO4-labeled macromolecules representing newly synthesized proteoglycans in bovine articular cartilage. The suppressed proteoglycan synthesis was due to the presence of NO. Conclusion These findings support the hypothesis that a component of S aureus can stimulate iNOS in articular cartilage, and that NO generated from this enzyme down-regulates cartilage matrix proteoglycan synthesis.