Fibronectin metabolism of cartilage explants in response to the frequency of intermittent loading

Chondrocytes within articular cartilage experience complete unloading between loading cycles and in so doing utilize mechanical signals to regulate their own metabolic activities. A strongly elevated fibronectin content is an early feature in osteoarthritis and appears to be related to increases in both the synthesis and retention of this glycoprotein. The objectives of this study were to investigate systematically whether the frequency of intermittently applied cyclic mechanical loading of cartilage explants alters the biosynthesis and retention of fibronectin, and to assess whether it is possible to induce in vitro osteoarthritic-like changes of this metabolic parameter by mechanical means over a period of 6 days. Cartilage plugs consisting of viability-checked chondrocytes were exposed to sinusoidal cyclic compressive pressure alterations of 0.1, 0.5 or 1.0 Hz frequency with a peak stress of 0.5 MPa for a period of 5, 10 or 20 s, followed by an unloading period of 10, 100 or 1000 s, and compared to unloaded reference plugs from the same joint and topographic origin. The incorporation of radioactive precursor into fibronectin during the last 18 h, the content of fibronectin, and the viability of chondrocytes were determined. Our data revealed that (a) the fibronectin synthesis was selectively, but non-linearly affected by the frequency of intermittent loads applied (as defined by the frequency of the applied force, the duration of the loading cycle and the duration of the force-free period between each loading cycle), and that (b) the retention of endogenous fibronectin and proteins within loaded cartilage explants is strongly elevated. These data support our hypothesis that the mechanical factor "frequency of intermittent loading" seems to be the crucial mechanical parameter controlling the metabolism of chondrocytes. The effect of the frequency of intermittent loading cannot be described by a simple statistical correlation, so that no specific predictions are possible. However, our results imply that distinct loading protocols have been established that can induce alterations of the fibronectin metabolism similar to those observed in human and animal osteoarthritis.