CENTRIFUGAL AND BIOCHEMICAL-COMPARISON OF PROTEOGLYCAN AGGREGATES HORN ARTICULAR-CARTILAGE IN EXPERIMENTAL JOINT DISUSE AND JOINT INSTABILITY

Two models involving altered joint loading were compared with regard t o their effects on the biochemical composition and proteoglycan aggreg ate structure of articular cartilage. Disuse atrophy was created in gr eyhound dogs by nonrigid immobilization of the right knee in 90 degree s of flexion, and joint instability was created by transection of the anterior cruciate ligament. Similarities and differences between the t wo experimental groups at two different time periods were examined to investigate why joint instability induces progressive and irreversible changes to the articular cartilage, whereas joint disuse induces chan ges that may be reversible when the joint is remobilized. The followin g studies were performed on the cartilage from all experimental and co ntrol groups: (a) compositional analyses to determine water, uronate, and hydroxyproline contents; (b) high performance liquid chromatograph y for detection of hyaluronan and chondroitin sulfates; and (c) centri fugation analyses of nondissociatively extracted and purified proteogl ycans to isolate and quantify the populations of monomers and slow and fast-sedimenting families of aggregates. In general, all cartilage wa s found to have a decreased ratio of proteoglycan to collagen after 4 weeks of disuse, and this ratio returned to control values at 8 weeks. In contrast, cartilage had an elevated ratio of proteoglycan to colla gen as well as increased hydration at 12 weeks after transection of th e anterior cruciate ligament. The most striking contrast between the t wo models was the finding of an approximately 80% decrease in the cont ent of hyaluronan at both time periods after transection of the anteri or cruciate ligament, with no evidence of a change after disuse. The r esults of centrifugation analyses indicated a significant decrease in the quantity of proteoglycan aggregates in both models. However, this decrease was associated primarily with a loss of slow-sedimenting aggr egates after disuse and a loss of both slow and fast-sedimenting aggre gates after transection of the anterior cruciate ligament. Furthermore , the population of fast-sedimenting aggregates was depleted to a grea ter extent than that of the slow-sedimenting aggregates. The preservat ion of fast-sedimenting aggregates as well as hyaluronan after periods of joint disuse but not joint instability suggests a possible mechani sm for the reversibility of cartilage changes. Although the proteoglyc an aggregates were depleted after disuse atrophy, it is possible that an aggregate-depleted matrix could recover when normal proteoglycan sy nthesis is resumed. In contrast, although synthesis may be maintained or elevated after transection of the anterior cruciate ligament, the m atrix may not be repopulated with aggregates because there is an insuf ficient amount of hyaluronan.