A morphological and immunohistochemical study in knee articular cartilage of patients with osteoarthritis

Osteoarthritis (OA), one of the most common skeletal disorders, characterized by joint cartilage degradation, is induced by accumulated mechanicals stress; however little is known about the underlying molecular mechanism. Thus the present study was conduced in order to deep inside these molecular changes, in particular by analysing the apoptotic cascade in knee articular cartilage of patients with OA.Articular cartilage specimens harvest from 10 patients with knee OA were assessed by histology (E-E, Masson Trichromic) histochemistry (Alcian Blue) and immunohistochemistry for Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), its death receptor DR5 and Caspase-3. Apoptotic condrocytes were detected by Terminal Deoxynucleotidyl Transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL).Histology and histochemistry results demonstrated the present of matrix calcification onset attended by proteoglycans reduction, respectively.The results showed an overexpression of DR5 receptor, its ligand (TRAIL) and caspase-3 in injured cartilage suggesting the activation of programmed cell death, however this cellular mechanism of death was not demonstrated by TUNEL-positive cells. The data could be interpreted considering an activation of cell apoptosis as a result of the cartilage injury, and confirmed by caspase-3 activation; however the discrepancy between apoptotic immunoexpression proteins (TRAIL, DR5) with increased caspase-3 activity on one side and negative TUNEL staining on the other may be explained by intracellular counter-regulative processes (posttranscriptional gene silencing or posttraslational enzyme inhibition by anticaspases) and thus apoptosis may be finally prevented. This last event may be considered a sort of protection mechanism after sublethal injury, in particular represented by an increased survival of condrocytes that are able to participate in the repair process.