DEGENERATIVE JOINT DISEASE IN DIABETES

糖尿病的临床并发症表现在两个骨骼 和非骨骼结缔组织。 尽管有大量的文献 与在非骨骼组织中观察到的并发症有关， 糖尿病，骨和软骨中发生的代谢变化， 很少受到关注。 根据我们目前的建议， 在长期糖尿病中，关节软骨经历形态学和 与退行性关节疾病中观察到的代谢变化相似。 这些变化在短期糖尿病软骨中不明显。 在这 建议我们计划检查的化学和物理特性， 从对照、糖尿病大鼠关节软骨中获得的蛋白聚糖 和胰岛素治疗的糖尿病动物在9个月的时间内。 软骨 蛋白聚糖将被分离和表征，使用新开发的 半微量程序，特别是开发的研究概述， 这个提议。 此外，最近开发的免疫程序 其使用特异性识别蛋白聚糖的单克隆抗体 聚合子结构将用于识别和定量 正常和实验性关节软骨中蛋白多糖成分 动物 生长于环境中的Swarm大鼠软骨肉瘤的蛋白多糖代谢 对照、糖尿病和胰岛素治疗的糖尿病动物也将 研究了 在这些研究中，大量的材料将可用于 在每一种中产生的蛋白聚糖的详细生物化学表征 实验动物 体内和体外掺入 将研究放射性标记的代谢前体，以确定 蛋白多糖合成速率受糖尿病患者的 条件 半微量分离程序将用于表征 新合成的蛋白聚糖和免疫程序， 由表征的单克隆抗体制备物制成的亲和柱 将被用来定量的特定的合成速率的任何变化， 蛋白多糖组分。 这项建议的长远目标是 将这些研究扩展到其他组织中蛋白多糖代谢的检查， 糖尿病中更复杂的结缔组织（如主动脉、眼睛和皮肤） 看看是否发生了任何变化， 在疾病的后期阶段变得明显的并发症。

The clinical complications of diabetes manifest themselves in both skeletal and non-skeletal connective tissue. Despite the extensive literature relating to the complications observed for non-skeletal tissues in diabetes, the metabolic changes occurring in bone and cartilage have received little attention. Studies from our current proposal suggest that in long-term diabetes articular cartilage undergoes morphological and metabolic changes similar to those observed in degenerative joint disease. These changes are not apparent in short-term diabetic cartilage. In this proposal we plan to examine the chemical and physical characteristics of proteoglycans obtained from rat articular cartilage of control, diabetic and insulin-treated diabetic animals over a nine month period. Cartilage proteoglycans will be isolated and characterized using newly developed semi-micro procedures particularly developed for the studies outlined in this proposal. In addition, recently developed immunological procedures which use monoclonal antibodies that specifically recognize proteoglycan aggregate substructures will be used to identify and quantitate proteoglycan components in articular cartilage from normal and experimental animals. Proteoglycan metabolism in Swarm rat chondrosarcomas grown in control, diabetic and insulin-treated diabetic animals will also be studied. In these studies, large amounts of material will be available for detailed biochemical characterization of proteoglycans produced in each experimental animal. The in vivo and in vitro incorporation of radiolabelled metabolic precursors will be studied to determine whether the rate of proteoglycan synthesis is significantly affected by the diabetic condition. Semi-micro isolation procedures will be used to characterize the newly synthesized proteoglycans and immunological procedures using affinity columns made from characterized monoclonal antibody preparations will be used to quantitate any changes in the rate of synthesis of specific proteoglycan components. The long-term objective of this proposal is to extend these studies to the examination of proteoglycan metabolism in other more complex connective tissue in diabetes (e.g. aorta, the eye and skin) to see if any changes occur which contribute significantly to the complications that become evident in the later stages of the disease.