Metabolic studies on connective tissue collagens in bone and tendon of adjuvant arthritic rat

The metabolic alterations in the matrix of connective tissue collagen were investigated in bone and tendon of rats with adjuvant-induced arthritis. Adjuvant arthritis was induced in rats with the immunization of Freund's adjuvant containing heat-killed Mycobacterium tuberculosis. The changes in the metabolism of collagen were studied using radioactive isotopic measurements with (3H)-proline. Tissue specimens were fractionated individually into soluble and insoluble collagens. The synthesis of collagen was examined by measuring the total collagen content and the radioactivity of (3H)-hydroxyproline in soluble collagen fraction within 24 hours after the administration of tritiated proline. The conversion of soluble to insoluble collagen was analyzed by measuring the radioactivity of (3H)-hydroxyproline in both soluble and insoluble collagens. The catabolism of soluble and insoluble collagens was studied by estimating the radioactivity of urinary (3H)-hydroxyproline 24 hours after the injection of tritiated proline. It was observed that the total collagen content and the total radioactivity of (3H)-hydroxyproline in bone and tendon were decreased significantly in adjuvant arthritic rats. The specific and total radioactivities of (3H)-hydroxyproline in soluble collagen were found to be reduced, indicating the decreased de novo synthesis of collagen during the diseased state. The conversion of soluble to insoluble collagen was impaired in tissues as evidenced by the increased content of soluble collagen in arthritic disease. In addition, an enhanced excretion of hydroxyproline was found in urine of arthritic rats, indicating the increased degradation of collagen in arthritic disease. These observations could, therefore, explain in part the changes in synthesis and degradation of collagen in bone and tendon during the development of experimentally induced adjuvant arthritis in rats.