Role of tumor necrosis factor-alpha converting enzyme in production of TNF-alpha by osteoarthritic articular chondrocytes

ABSTRACT

The study was conducted to find out the expression and function of TNF-alpha converting enzyme [TACE] in the articular cartilage of osteoarthritis [OA] patients. The cartilage was examined to investigate the post-translational regulation of TNF- alpha production by TACE in those OA patients. RT-PCR for TACE and TNF- alpha mRNA were performed on articular cartilages from 38 OA patients and 20 healthy controls. The function of TACE in OA affected cartilages was investigated by using TACE inhibitor, which was added in different concentrations to OA cartilage organ cultures and the released cytokines and soluble cytokine receptor in culture supernants were measured with ELISA. Expression of TACE and TNF- alpha mRNA by RT-PCR was detected in all OA affected cartilages, but not in normal cartilages. TACE inhibitor in high concentrations significantly reduced the release of TNF- alpha, sTNF-RII and IL-8 from chondrocytes from OA patients and normal peripheral blood monocytes from healthy controls. TACE is an important regulator of the secretion of TNF- alpha from articular chondrocytes of OA patients