Behaviour of nitric oxide synthase isoforms in inflammatory human joint diseases: an immunohistochemical study

Nitric oxide (NO) is produced by nitric oxide synthases (NOS) expressed in various human tissues and, depending on the amount of NO produced in each tissue, the physiological function of NO is determined. Since increased inducibile nitric oxide synthase (iNOS) expression and NO generation are associated with pathogenesis of idiopatic osteoarthritis of synovial tissue and data about constitutive nitric oxide isoform (cNOS) in this tissue are scarce, in this study we investigated the localization and distribution of nitric oxide isoforms in normal, acute and chronic diseased synovium. The immunohistochemical and histologic analysis was performed in human synovial tissue obtained from 10 patients with post-traumatic inflammation, 14 patients with idiopatic osteoarthritis and normal synovial specimens were obtained from 7 patients undergoing surgery for reconstruction of the anterior cruciate ligament. Immunohistochemical data showed iNOS was strongly expressed in the synovial lining layer, subsynovium and blood vessels from patients with acute and chronic inflammation pathology, on the contrary, normal joints were negative. A similar pattern of cNOS immunoreactivity was seen in synovial lining and vascular smooth muscle in the pathological samples, while in the normal joint the intensity of staining was weaker than the inflammed. These data indicate that NO is produced locally in the pathological synovial lining not only by iNOS but also by cNOS.