Mechanical loading of articular cartilage can produce catabolic and anabolic changes in tissue metabolism. Most previous studies in this area have focussed on aggrecan. Little information concerning load-induced collagen modifications has been obtained. We have therefore conducted studies where mechanical loads are applied in vitro to full thickness cartilage explants retaining a thin layer of bone, in order to investigate mechanically induced collagen breakdown and consequent turnover, in addition to aggrecan changes and mechanical property alterations. Tissue explant disks were subjected to unconfined compression and either immediately frozen or kept in static culture for 10 days. Mechanical tests of the disks immediately prior to and just after the cyclic loading period were also performed. They showed a weakening of the collagen network and an increased hydraulic permeability due to the cyclic loading. Load-induced alterations of the extracellular matrix was then clearly evidenced by an increase in denatured collagen in the disks frozen immediately after loading compared to unloaded controls. Loaded disks maintained in culture for 10 additional days following cyclic loading no longer expressed this increase in denatured collagen suggesting that mechanically denatured collagen II had undergone a removal process which could represent turnover or repair, or the beginning of progressive degradation. Indeed matrix fragments of collagen II and glycosaminoglycans were found to be released to post-loading culture medium in increased quantities compared to unloaded controls. Our data further demonstrates the ability of mechanical load of articular cartilage to modulate turnover and metabolism of collagen and proteoglycan in a complex and multifactorial manner that may be of particular significance in the pathogenesis of osteoarthritis and in the development of pharmacological agents to modulate its progression.