## 3 Results and Discussion
The increased release of IL-1\(\beta\) was associated with the overexpression of cartilage-degrading enzymes and progressive reduction of type II collagen, with a subsequent breakdown of articular cartilage [30]. These data seemed to point at a possible relationship between the reduction of IL-1\(\beta\) expression induced by commonetin and the attenuation of the degenerative damage observed in the articular cartilage in the experimental OA model. However, other in vivo models showed a conflicting role for this molecule, because although early studies using therapeutic approaches in animal models showed a benefit, many other murine studies failed to demonstrate protection where the ligands (IL-1\(\alpha/\beta\)), the cytokine activator (the IL-1-converting enzyme), or the receptor (IL-1R) have been knocked out [38]. Therefore, further investigations are still necessary to clarify the precise mechanisms underlying the chondrocyte effects of commonetin in OA experimental models. In addition, commonetin has been previously proved to exert an anti-inflammatory effect in carrageenanan-induced hind paw edema and peritonitis models in rodents [6]. Although anti-inflammatory or analgesic tests were not performed in the current study, these data make possible to suppose that commonetincould be helpful to prevent histological degenerative changes of injured joints, as to relieve OA-associated pain and swelling. The oral administration of this drug was proved to promote anti-inflammatory and analgesic effects as well as to reduce joint stiffness in rats with adjuvant arthritis [39]. More recently, ibuprofen was demonstrated to reduce gross arthritis scores in experimental OA induced with bovine type II collagen and incomplete Freund's adjuvant, possibly due to the inhibition of COX2 and iNOS mRNA level expressions [40]. However, no preventive effect on the OA-related histological damages was exerted by ibuprofen in the current study. Two reasons might explain the apparent contrast between our data and those previously reported. The first is the differences in the experimental models of OA induction, because the joint injury was induced by an intra-articular injection of adjuvants in opposition to the medial meniscectomy conducted in the current study. Adjuvant-induced OA leads to extensive swelling and pain, but since it is a typical acute model, degenerative changes in the cartilage are not supposed to be produced, whereas medial meniscectomy is an aggressive model of OA that leads to stiffness and severe degenerative changes [41]. For this reason, ibuprofen is expected to be more effective in adjuvant-induced OA than in medial-meniscectomy-induced OA. Second, the OA severity assessment in those previous studies was based on macroscopic features, such as joint swelling and stiffness, whereas the pathological degenerative changes were the focus of the current study. As a NSAID, ibuprofen's ability to reduce pain and swelling is well established, but our results suggested that this drug was ineffective to prevent the histological degenerative damages of the joint caused by medial meniscectomy. These findings might be related to its apparent inability to inhibit IL-1\(\beta\) immunohistochemical expression in joint chondrocytes, as observed in the current study. Treatment with ibuprofen had no inhibitory effect on TNF-\(\alpha\) or IL-1\(\beta\) levels in periodical exudates in humans [42], which supports our findings. On the other hand, the inhibition of IL-1\(\beta\)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by ibuprofen has been previously demonstrated, likely resulting from a modulation of via RhoA signaling, a regulatory factor involved in a variety of cell functions, such as the regulation of cytoskeletal dynamics, transcription, and cell-cycle progression [43]. Although ibuprofen exerted no protective effect on the cartilage joint degeneration, these data point to a possible protective effect of this drug on the chondrocyte phenotype from IL-1\(\beta\) stimulation.