Ad-TRAIL Induces Apoptosis in Chondrocytes in Vitro and Neutralizing Antibody to TRAIL Prevents The Induction of Apoptosis in Vitro and in Vivo / 대한해부학회지

ABSTRACT

We undertook this study to investigate whether tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)implicates in the pathogenesis of osteoarthritis (OA). Expression of TRAIL, and death and decoy receptors was examined on the primary cultured chondrocytes and the cartilage obtained from experimentally-induced OA rat model by immunohistochemistry. In vitro and in vivo blocking experiments with anti-TRAIL neutralizing antibody were conducted, and the prevention of cell death was determined by TUNEL assay. Ad-TRAIL infection induced expression of TRAIL and increased expression of death receptor DR4, and decreased expression of DR5 and DcR1 in primary cultured rat chondrocytes. Ad-TRAIL, at 10 and 100 MOI doses, decreased viability of chondrocytes on 4 days after infection. The cartilage obtained from chemically induced OA rat model showed the increased expression of TRAIL and DR4, and the decreased expression of DR5 and DcR1. Whereas surgically induced OA cartilage in vivo showed the increased expression of TRAIL, and DR4 &5 and the decreased expression of DcR1, compared to the control cartilage. In vitro blocking experiment prevented partially Ad-TRAIL induced death of chondrocytes. Furthermore, in vivo blocking experiment also partially prevented apoptosis in two in vivo OA models. In conclusion, TRAIL-induced chondrocyte apoptosis may play a role in pathogenesis of osteoarthritis.