Role of transglutaminase 2 in apoptosis induced by hydrogen peroxide in human chondrocytes.

Chondrocyte apoptosis has been implicated in the pathogenesis of osteoarthritis. Transglutaminase 2 (TG2), the expression of which is higher in osteoarthritis patients, has been shown to be up-regulated during apoptosis in many experimental models. This study investigated the expression and role of TG2 in human chondrocytes undergoing apoptosis induced by hydrogen peroxide (H₂O₂). Human chondrocytes were obtained from the knee articular cartilage of patients undergoing total joint arthroplasty. Apoptosis was induced by H₂O₂ and was measured with Annexin-V flow cytometry, DNA Fragmentation ELISA and DAPI staining. Western Blot, an in situ activity assay and immunocytochemistry were used to examine TG2 expression. The role of TG2 was evaluated by TG-specific siRNA transfection and monodansylcadaverine (MDC), a competitive substrate for TG2. H₂O₂ induced apoptosis of human chondrocytes in a dose- and time-dependent manner. The level of TG2 expression was higher in the chondrocytes undergoing H₂O₂-induced apoptosis. Inhibition of TG2 by siRNA or MDC increased the level of apoptosis in the H₂O₂-treated chondrocytes. TG2 expression is higher in human chondrocytes undergoing apoptosis, and inhibition of TG2 leads to increased apoptosis. These results may raise the possibility of TG2 as a modulator of cartilage damage in osteoarthritis by offering protection against chondrocyte apoptosis.

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