The prevalence of nitric oxide in apoptotic chondrocytes of osteoarthritis.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Gadolinium inhibits thymidine incorporation and induces apoptosis in chondrocytes.

Magnetic resonance arthrography. a procedure where contrast agents containing gadolinium are administered intra-articularly, has become a useful tool in musculoskeletal diagnosis. Although considered safe for systemic use, toxicities in some tissues have been identified for both free gadolinium ion and the gadolinium chelates used as contrast. In this study, the effects of short-term exposure of articular chondrocytes to gadolinium contrast were examined by assaying for proteoglycan synthesis, cell proliferation, and apoptosis. Bovine chondrocytes were grown in monolayer culture and exposed to gadodiamide for 16 h. Proteoglycan synthesis was measured through incorporation of radiolabeled sulfate. Uptake of radiolabeled thymidine assessed cell proliferation. Apoptosis was detected using the TUNEL assay, where DNA strand breaks characteristic of apoptosis are labeled with fluorescent nucleotide. Proteoglycan synthesis was stimulated by lower dose exposure to gadodiamide. At higher doses, proteoglycan synthesis returned to baseline. Cell proliferation decreased following exposure to gadodiamide in a dose-dependent manner. Chondrocyte apoptosis was induced in a dose-dependent manner. Further work is needed to determine if these in vitro effects are present in the intact joint.

A comparison of MRI findings in patients with acute and chronic ACL tears.

This retrospective study compared the magnetic resonance imaging (MRI) findings in 87 patients with acute and chronic anterior cruciate ligament (ACL) tears. Sixty patients had acute tears and 27 had chronic tears. The appearance of the torn ligament was examined on MRI, and associated meniscal and osteochondral injuries were described. All findings were verified at arthroscopy. Acute ACL tears (MRI examination was performed within 6 weeks of injury) were typified by the presence of diffuse (58%) or focal (42%) increased signal within the ligament, whereas chronic ACL tears (MRI examination was performed more than 6 months after injury) usually appeared as either a fragmented ligament (44%) or an intact band of low signal with abnormal orientation (30%). Patients with chronic ACL tears had a higher prevalence of medial meniscal tears (78% versus 40%), articular chondromalacia, and an increased posterior cruciate bow ratio (0.47 versus 0.37) in association with chronic ACL tears. A bone bruise was seen in 68% of acute ACL tears but in no case of chronic ACL tear. On MRI, there are salient differences between acute and chronic ACL tears. Chronic ACL tears are associated with a greater prevalence of meniscal and osteochondral injuries. These findings may have implications for future treatment recommendations.