Apoptosis appears to be a significant mechanism of chondrocyte death in osteoarthritis (OA). There is increasing evidence that nitric oxide (NO) may be the inducing signal for apoptosis, but no study has definitively shown an association between the two in vivo. In this study, sections of osteoarthritic cartilage were double stained for the presence of apoptosis and NO to test the hypothesis that NO is the inducer of apoptosis in arthritis.
Sections of osteoarthritic cartilage obtained during total knee arthroplasty were stained for apoptosis with terminal transferase-mediated dUTP nick end labeling (TUNEL). The sections were then stained for nitrotyrosine (a marker of NO production) by immunohistochemistry. The prevalence of NO in cells positive for apoptosis and in cells negative for apoptosis was determined by fluorescent microscopy.
The prevalence of NO in apoptotic cells was no different than in non-apoptotic cells, suggesting NO is not the initiating signal for apoptosis in vivo.
The precipitating cause for apoptosis in arthritic chondrocytes has not yet been determined. The data from this study fail to support NO as the direct initiating signal. NO synthase inhibitors may still be useful in the treatment of OA by blocking the catabolic activities of NO.