Naproxen treatment inhibits articular cartilage loss in a rat model of osteoarthritis

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.

Human Mesenchymal Stem Cell‐Derived Miniature Joint System for Disease Modeling and Drug Testing

“…In our study, we observed chondroprotective effects of NPX treatment using histological staining (Figure 7e ), which agrees with a recent study where NPX treatment was found to reduce the loss of articular cartilage in the rat DMM model. [ 46 ] However, the transcriptome in chondrocytes was not significantly influenced by NPX, supporting the findings by Mastbergen et al. [ 44 ] Instead of playing a direct role on chondrocytes, naproxen may function through suppressing the inflammation of “synovial tissue” in the miniJoint and reducing the release of pro‐inflammatory cytokines and degradative enzymes to the SM (Figure 7c ).…”

NSAIDs Reduce Therapeutic Efficacy of Mesenchymal Stromal Cell Therapy in a Rodent Model of Posttraumatic Osteoarthritis

“…27 Similarly, cultured cartilage explants harvested from patients who used NSAIDs daily for 4 weeks before total joint replacement surgery had increased proteoglycan synthesis rates compared with those who did not receive NSAIDs. 7 Preclinical studies using instability 37 and collagenase-induced 20 OA rodent models observed decreased damage when treating animals with naproxen. Disease modification with NSAID use, however, has not yet been observed clinically.…”

Comparative Chondroprotective Effects of Intra-Articular Hyaluronic Acid and Triamcinolone in Murine Model of Osteoarthritis

“…Before surgery rats were anesthetized with intraperitoneal injection of 5% xylazine and 1% ketamine. 8 Right knee joint of rats was shaved and disinfected in a sterilized environment. After that, a para-patellar incision was made on medial side for complete joint exposure.…”