The proposed study examines the ability of normal articular cartilage to alter its metabolism, and the composition of its matrix, in response to local changes in joint loading. A non-invasive, physiologic exercise protocol has been developed which has been shown to alter loading in the canine humeral head. In this model, dogs are walked daily in an exercise carousel, with a series of low steps placed in the exercise path. Kinematic analyses have shown that dismounting the steps induces compressive loading in the caudal-central region of the humeral head, which is normally unloaded. Notably, it is also the site in which osteoarthritis of the shoulder develops in aging dogs. Histochemical studies of cartilage from dogs placed on the step-walking protocol for 6 months suggest that an increase in chondroitin sulfate content occurs in the lesion-prone caudal-central region, while cartilage from the dorsal plateau remains histochemically normal. In the proposed study the apparent modulation in glycosaminoglycan content of cartilage resulting from this exercise regimen will be studied chronologically, and and attempt will be made to confirm the histochemical findings by biochemical and metabolic studies. Six control dogs will be permitted only limited exercise. Eighteen dogs will be exercised by walking over a flat path for 1, 3 or 6 months (6 dogs/time period), while a third group of 18 dogs will be similarly exercised over a path containing low steps for 1, 3 or 6 months. At sacrifice, cartilage from the dorsal plateau and caudal-central regions of each humeral head will be obtained for histochemical studies, and for analyses of water, uronic acid and collagen contents, and glucosamine:galactosamine molar ratios (to measure ratios of keratan sulfate: chonodroitin sulfate). In addition, the influence of the altered load pattern on glycosaminoglycan synthesis and degradation, and on the hydrodynamic size of newly-synthesized and total tissue proteoglycan subunits and aggregates will be studied. The data should help elucidate the relationships which exist in this model between alterations in load and chondrocyte metabolism, and may serve as a basis for understanding the role of mechanical factors in maintaining the integrity of articular cartilage, or in facilitating its breakdown.
