This study describes the effect of load magnitude, frequency and duration on proteoglycan (PG) biosynthesis and loss in mature bovine articular cartilage explants. Cultured full thickness cartilage discs were subjected to a continuously applied, uniaxial compressive cyclic load. The loads were applied using a sinusoidal waveform of 0.001, 0.01, 0.1 or 0.5 Hz-frequency and a peak, stress of 0.1, 1.0, 2.5, or 5.0 MPa for a period of 1, 3 or 6 days. Increasing the load magnitude, as well as the duration of loading, reduced the PG biosynthesis. Reducing the load frequency abolished the inhibitory effect of a given load magnitude on PG biosynthesis, even though explants mere more compressed. Increasing the load magnitude stimulated the release of newly synthesized PGs from explants, whereas an elevated duration of loading significantly decreased the release of endogenous PGs. Explants loaded for 1 or 3 days were viable as determined biochemically, whereas 6 days of loading resulted in a slightly diminished viability of explants. This study demonstrates that the duration and intensity of loading influences the inhibition of PG biosynthesis, while PG loss is only modulated by the magnitude and duration of loading. (C) 1997 Academic Press.