Non-calcified cartilage. Previous studies revealed the beneficial effect of this drug

A possible explanation could be the The evaluation from the linguistic qualities of patients employing many Net substantial variability due to the use of a qualitative subjective scoring system for their evaluation; another explanation (comparing these results with the calcified samples) could be that due to decalcification the integrity of the samples (chiefly bone and calcified cartilage) title= per.1944 may have been altered [24]. Previous studies revealed the beneficial effect of this drug not only for cartilage protection, but also for synovitis and reduction in bone erosion in a mice model of inflammatory arthritis [41]. The mechanisms of the antiinflammatory effect of diacerein have not yet been completely clarified but Tamura et al. (2002) [42] demonstrated, using inflammatory animal models, a different spectrum of anti-inflammatory activity of diacerein than those of NSAIDs, which may be due to the inhibition of IL-1 and the production of reactive oxygen species [42, 43]. The histologic evaluation of the synovial membrane in the OA group revealed moderate to severe inflammatory changes with thickening of the lining cell layer, hyperplasia and infiltration with inflammatory cells. In the diacerein-treated group (OA + DC) these changes are milder than in the OA group, although, as in a canine cruciate-deficiency model [12] the results are not statistically significant, as the animals of this OA + DC group obtained values halfway between healthy and osteoarthritic ones. The same results were observed inthe cartilage, where a reduction of the thickness is observed in treated animals with respect to the OA group. In the paraffin-embedded samples there were no differences between groups (although the cartilage pathology is almost significant). A possible explanation could be the substantial variability due to the use of a qualitative subjective scoring system for their evaluation; another explanation (comparing these results with the calcified samples) could be that due to decalcification the integrity of the samples (chiefly bone and calcified cartilage) title= per.1944 may have been altered [24]. However, in decalcified samples, the results for the OA + DC group were closer to normality than those obtained for the OA group. In the samples evaluated by a histomorphometric quantitative methodology, results showed improvement in the diacerein-treated group compared to the one treated with placebo, although differences were not significant. In cartilage parameters there were statistical differences in Cg.Th and nCg.Th between the OA group and the CTRL + DC group and for the latter also with the CTRL group. There were no differences between OA and OA + DC, but nor between OA + DC and CTRL + DC and the tendency of values was to approximate joint values to normal. Regarding FI -an important parameter because it makes a clear distinction between ill and healthy animals [44]- there were no statistical differences between groups, but there title= fnins.2013.00251 is a tendency of approximating values of OA + DC to those of controls. The results obtained from the undecalcified samples were better than those from the decalcified ones because of a better conservation of the tissue structure and because the computer evaluation has a greater degree of objectivity, accuracy and reproducibility, as well as the micro-CT [24], with comparable results between both. In our study, the subchondral bone showed no statistical differences, so further studies may be needed in this regard. Micro-CT data have shown an anabolic effect of diacerein on subchondral trabecular microstructure in both healthy and osteoarthritic samples (though less pronounced in the latter).