Blocking Tnf Alpha Attenuates Progressive Cartilage Matrix Degradation In Inflammatory Arthritis

Because damage to hyaline cartilage is irreversible, relieving progressive cartilage destruction is an important therapeutic approach for inflammatory arthritis. In the present study, human hyaline chondrocytes were isolated from total knee replacements of 15 patients with osteoarthritis (OA) and three with rheumatoid arthritis (RA). Synovial fluid of OA (n=25) and RA (n=34) were collected to measure tumor necrosis factor alpha (TNF alpha) using ELISA. Consistent with previous studies, the synovial fluid exhibited high TNF alpha levels and hyaline cartilage was severely destroyed in patients with RA. TNF alpha-treated chondrocytes were used as model for inflammatory arthritis. TNF alpha did not influence proliferation or extracellular matrix expression in chondrocytes, but induced matrix metalloproteinase (MMP)1, 3 and 13 expression levels in chondrocytes, which was accompanied by activation of nuclear factor-kappa B signaling. During chondrogenic differentiation, TNF alpha attenuated mRNA expression levels of anabolic factors (collagen type 2 and aggrecan) and enhanced mRNA expression of catabolic factors (MMP1, MMP3 and MMP13) in chondrocytes. Moreover, anti-TNF alpha agents (Golimumab) inhibited the TNF alpha-induced metabolic shift in chondrocytes and chondrogenic differentiation. The present study revealed a mechanism by which TNF alpha may induce metabolic shift in chondrocytes, leading to progressive chondrocyte destruction.