Evaluation of chondrocyte growth and function subjected to 21% and 6% oxygen levels.

In osteoarthritis, the metabolic activity of the chondrocytes is shifted toward a state where new matrix synthesis is outweighed by breakdown of matrix constituents. The result is degeneration and gradual loss of articular cartilage. Although osteoarthritis is frequently regarded as a non-inflammatory form of arthritis, considerable data implicates a role for pro-inflammatory cytokines in the cartilage destruction associated with osteoarthritis. The best studied pro-inflammatory cytokines in osteoarthritis are interleukin-1ß (IL-1ß), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6). Since articular cartilage is not vascularized, it must rely on diffusion from the articular surface for nutrient and metabolic exchange. Consequently, the entire metabolism of the cell is geared towards operating at a low oxygen tension. In this study, chondrocytes were challenged with pro-inflammatory cytokines at 21% O2 and 6% O2. Chondrocyte proliferation, membrane integrity, oxidative stress, matrix metalloproteinase – 9 (MMP-9) and hypoxia inducible factor-1a (HIF-1a) production were measured. Our results showed that there was less of a decrease in cell number at 6% O2 compared to 21% O2 after they were challenged with pro-inflammatory cytokines. In addition, there was less of an increase in oxidative stress, membrane damage and MMP-9 production at 6% O2 compared to21% O2. The significance of this study represents the first attempt to replicate a diseased inflammatory environment characterized by an osteoarthritic joint in vitro and to examine these effects on the growth and stability of chondrocytes.