The Effects Of Highly Selective NSAIDS On Osteoarthritic Cartilage In The Experimental Rat Model

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used commonly to manage the pain and inflammation associated with osteoarthritis. Studies verified that NSAIDs had favourable or detrimental action on OA progression, even the same NSAIDs had reverse effects on articular cartilage in different studies. Highly selective NSAIDs (Celecoxib and Rofecoxib) are a new class of analgesic agents that posses the analgesic and anti-inflammatory efficacy of conventional NSAIDs, but without many of their side effects. So far, there are no convincing data to show the widely used NSAIDs and recommended highly selective COX-2 inhibitor have favourable effects on cartilage. Therefore, it is necessary and valuable to clarify the effects of these NSAIDs on cartilage in OA. In this study we evaluated the chondrotoxic effects of some NSAIDs on articular cartilage in an experimental model of osteoarthritis (OA). We investigated the potential effects of highly selective NSAIDs (HSNSAIDs) on osteoarthritic cartilage integrity and compared with ibuprofen, indomethacin and normal saline.161 Wistar rats weighing 0.15kg and 3 or 4 months old were chosen. The left knee osteoarthritis was induced after surgery two months later by the excision of the left achilles tendon. Wistar rats were randomly divided into 5 groups: Celecoxib (CE) group, Ibuprofen (IBP) group, Indomethacin (IN) group, Normal saline (NS) group and Rofecoxib (RO) group. Celecoxib were given by orally at dosage of 24mg.kg-1day-1. And ibuprofen (72mg.kg-1.day-1), indomethcin (9mg.kg-1.day-1), rofecoxib (3mg.kg-1.day-1) were given. The rats in five groups were sacrificed in batches 3, 6 and9 months after the procedures. Histological evaluation on osteoarthritic cartilage of left knee joint were performed. The expression of collagen (type II, I and III), IL-18, IL-1a and TNF-a were tested by immunohistochemical staining. The chondrocytes apoptosis were measured by means of TUNEL.Celecoxib and rofecoxib were observed to have some beneficial influences on the articular cartilage. Celecoxib and rofecoxib reduced the OA-like histological changes and significantly protected the knee joint from OA-like change in experimental OA model. Celecoxib and rofecoxib had favourable action on OA progression by increasing the matrix component synthesis, inhibiting the degradation of proteoglycan, increasing the synthesis of collagen type II and I, suppressing the expression of IL-1 and TNF-a, and protecting the chondrocytes against apoptosis.Ibuprofen had a negative influence on joint structure and altered the physiological properties of the tissue. Ibuprofen caused a statistically significant increase in the severity of most of the osteoarthritic parameters. Ibuprofen inhibited the matrix component synthesis. And Ibuprofen increased the degradation of proteoglycan, the synthesis of collagen type II, I and III, and the expression of IL-1 and TNF-a. Ibuprofen enhanced the chondrocytes apoptosis.Indomethacin was found to have deleterious effects on articular cartilage. Indomethacin caused the damage of chondrocytes, erosion of articular cartilage, injury of surrounding tissue and eventually permanent loss of joint function. Indomethacin suppressed the proteoglycan synthesis, promoted IL-1 and TNF-a secretion. Indomethacin suppressed the synthesis of collagen type II, but increased the synthesis of collagen type I and III. And Indomethacin enhanced the chondrocytes apoptosis.The present study shows that celecoxib and rofecoxib, the highly selective COX-2 inhibitors, do not interfere with chondrocyte structure and function, and have cartilage-protective properties as it can restore the integrity of cartilage matrix under inflammatory conditions. The present results suggest that, in addition to its gastroprotective properties, celecoxib and rofecoxib may be the drugs of choice in the treatment of chronic destructive joint disease where anti-inflammatory drugs need to be used for a prolonged period. We conclude that, in the prescription of NSAIDs for OA, it would be appropriate to ch...