Nitric oxide production and apoptosis in cells of the meniscus during experimental osteoarthritis

Objective. To examine the pathologic changes in meniscus tissue during expe rimental osteoarthritis (OA) and to determine the relationship between nitr ic oxide (NO) synthesis, apoptosis, and meniscus degradation. Methods. OA was induced in rabbits by anterior cruciate ligament (ACL) tran section. Knees were harvested after 9 weeks and assessed for OA severity. M enisci were subjected to histologic, immunohistochemical, and electron micr oscopic analyses for the presence of nitrotyrosine and apoptosis. Menisci w ere also cultured for analysis of NO production. Results. All menisci from joints with ACL transection demonstrated degenera tive changes. a high number of apoptotic cells was present in the medial pa rt of menisci, which contains chondrocytic cells. Menisci from nonoperated contralateral knees contained only small numbers of cells in apoptosis. Con ditioned media from meniscus cultures contained similarly elevated levels o f nitrite as cartilage cultures from the same arthritic knees. Nitrotyrosin e immunoreactivity, an indicator of in vivo NO production, was prominent in menisci from knees with ACL transection. In addition, menisci from normal knees produced high levels of NO in response to in vitro stimulation with i nterleukin-1 beta or lipopolysaccharide. Conclusion. These observations suggest that pathologic changes in menisci a re a regular feature of experimentally induced OA and are associated with N O production and meniscus cell apoptosis.