In vitro rabbit articular cartilage organ model II. ³⁵S incorporation in various oxygen tensions

Abstract

Adult rabbit articular cartilage slice and plug explants were cultured in MEM/NCTC 109/fetal calf serum at 37°C in various oxygen tensions. In both the slice and plug explants, 85S04 incorporation exhibited a broad tolerance to oxygen tensions varying from 5 (38 mm. Hg) to 60 (456 mm Hg) per cent. Significantly (P 0.01) less 35S04 was incorporated in 1 (7.6 mm Hg) and 90% (684 mm Hg) oxygen than in 21 % (160 mm Hg) oxygen. No histologic or autoradiographic differences, and only slight histochemical differences, were discernible after seven days culture in the various oxygen tensions. It is suggested that low synovial fluid oxygen tension is detrimental to articular cartilage glycosaminoglycan metabolism. suggest that articular cartilage follows an anaerobic metabolic pathway (1-3). Glycolytic enzymes and high concentrations of lactic acid (1) are found in articular cartilage, and articular cartilage is little affected by short periods of oxygen deprivation (2), is relatively tolerant to high concentrations of potassium cyanide(3), and is very sensitive to monoiodoacetate (3), an agent that prevents glycolysis. Recent investigations (4-6) indicate that synovial fluid oxygen tensions decrease to very low levels in inflammatory joint diseases. These last studies present the possibility that synovial fluid hypoxia might cause chondrocyte damage and death.This report describes a series of experiments in which an in vitro articular cartilage model was cultured in various oxygen tensions. The results indicate that while articular cartilage sulfate incorporation is quite tolerant to rather wide variations in the prevailing oxygen tension, sulfate incorporation is significantly diminished at 1% and 90% oxygen.

Changes in synovial PO2 and blood flow in the rabbit knee joint due to stimulation of the posterior articular nerve.

“…If low PI,O2 values occur in the deeper parts of the joint under physiological conditions, this could have important consequences if the joint sustains injury or becomes diseased. In a rabbit in vitro articular cartilage model it was found that low PO2 was detrimental to cartilage glycosaminoglyean metabolism resulting in inhibition both of cellular proliferation and synthesis of extracellular ground substance (Brighton, Lane & Koh, 1974;Lane, Brighton & Menkowitz, 1977). If joint injury or disease caused still further reduction in P, 02' this could contribute to, or perhaps initiate, processes such as cartilage destruction, angiogenesis and fibroblast proliferation which are known to occur in conditions such as rheumatoid arthritis.…”

Chondrocytes

“…Nevertheless, while they tolerate very low oxygen tensions more successfully than do fibroblasts, chondrocytes do not thrive under such conditions. Synthetic activity is also reduced by very high oxygen tensions (Marcus, 1973;Brighton et al, 1974). Since cartilage cellularity varies over a wide range the glycolytic and respiratory rates (Table 1) of the whole tissue tend to reflect cell density.…”

Rapid effects of hypoxia on H+ homeostasis in articular chondrocytes

“…Possibly as a result of their low ambient O 2 , chondrocyte metabolism is almost entirely glycolytic. Nevertheless, removal of O 2 has marked effects, depressing both metabolism (reducing adenosine triphosphate (ATP) levels and lactate production-the negative Pasteur effect) almost immediately [17] and inhibiting matrix synthesis [2,7,12,40].…”