Mechanical loading of articular cartilage can influence chondrocyte metabolism and lead to alterations in cartilage matrix composition. Most previous studies have focused on the effect of cyclic loading on cartilage mechanical properties and proteoglycan (PG) synthesis. However, the role of PGs synthesized from cyclic loaded cartilage in response to an acute overloading has not been elucidated. We have therefore conducted studies where low intensity, intermittent cyclic loading was applied to chondral explants prior to an acute unconfined compression on the tissue. Chapter One documented a study by our laboratory showing that 14 days of intermittent cyclic loading on chondral explants has a positive effect on the tissue, by causing mechanical stiffening prior to a blunt force overloading, to limit acute tissue damage. And yet, longer term loading to 21 days results in tissue degradation prior to the acute traumatic event. In Chapter Two a supplement of glucosamine-chondroitin sulfate was used in an experimental setting to alter PG synthesis during cyclic loading of explants and its effect on the response of cartilage to an acute overload was documented. The results showed that experimentally increased tissue PGs during cyclic loading of cartilage help strengthen the cartilage, making them inhibit the degradation of the tissue after long-terrn cyclic compression and reduce the susceptibility of cartilage to a severe level of mechanical injury. In the long term these types of studies may help understand the role of biologic-based pre-conditioning of articular cartilage for in vitro, or even in vivo studies of blunt force trauma to a joint.