Abstract
The effects of naproxen, a nonsteroidal anti-inflammatory drug (NSAID), on articular cartilage degeneration in female Sprague-Dawley rats was examined. Osteoarthritis (OA) was induced by destabilization of the medial meniscus (DMM) in each knee. Rats were treated with acetaminophen (60 mg/kg), naproxen (8 mg/kg), or 1% carboxymethylcellulose (placebo) by oral gavage twice daily for 3 weeks, beginning 2 weeks after surgery. OA severity was assessed by histological Osteoarthritis Research Society International (OARSI) scoring and by measuring proximal tibia cartilage depth using contrast enhanced µCT (n = 6 per group) in specimens collected at 2, 5, and 7 weeks after surgery as well as on pristine knees. Medial cartilage OARSI scores from the DMM knees of naproxen-treated rats were statistically lower (i.e., better) than the medial cartilage OARSI scores from the DMM knees of placebo-treated rats at 5-weeks (8.7 ± 3.6 vs. 13.2 ± 2.4, p = 0.025) and 7-weeks (9.5 ± 1.2 vs. 12.5 ± 2.5, p = 0.024) after surgery. At 5 weeks after DMM surgery, medial articular cartilage depth in the proximal tibia specimens was significantly greater in the naproxen (1.78 ± 0.26 mm, p = 0.005) and acetaminophen (1.94 ± 0.12 mm, p < 0.001) treated rats as compared with placebo-treated rats (1.34 ± 0.24 mm). However, at 7 weeks (2 weeks after drug withdrawal), medial articular cartilage depth for acetaminophen-treated rats (1.36 ± 0.29 mm) was significantly reduced compared with specimens from the naproxen-treated rats (1.88 ± 0.14 mm; p = 0.004). The results indicate that naproxen treatment reduced articular cartilage degradation in the rat DMM model during and after naproxen treatment.