Tetracycline administration increases collagen synthesis in osteoblasts of streptozotocin-induced diabetic rats : a quantitative autoradiographic study

• Published in: Calcified tissue international 1992-05, Vol.50 (5), p.411-419
• Main Authors: SASAKI, T, RAMAMURTHY, N. S, GOLUB, L. M
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Autoradiography; Biological and medical sciences; Collagen - biosynthesis; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Male; Medical sciences; Microscopy, Electron; Miscellaneous. Antibiotics with multiple activities; Osteoblasts - metabolism; Osteoblasts - ultrastructure; Osteoporosis - etiology; Pharmacology. Drug treatments; Procollagen - metabolism; Proline - metabolism; Rats; Rats, Inbred Strains; Streptozocin; Tetracycline - pharmacology; Tetracycline - therapeutic use; Tritium
• ISSN: 0171-967X; 1432-0827
• DOI: 10.1007/BF00296771

Streptozotocin-induced, insulin-deficient diabetic rats were administrated either minocycline (MC) or a chemically modified non-antimicrobial tetracycline (CMT) by oral gavage for a 3-week period; untreated diabetic and nondiabetic rats served as controls. On day 21, all rats received an intravenous injection of 3H-proline followed by perfusion fixation with an aldehyde mixture at 20 minutes and 4 hours after isotope injection. The parietal bones of these rats were dissected and processed for quantitative electron microscopic autoradiography to study 3H-proline utilization by osteoblasts. At 20 minutes after 3H-proline injection, radioprecursor was incorporated by the Golgi-RER system of the osteoblasts in the periosteal surface of the control rats. At the 4-hour time period, most of the label was present over the collagen fibers of the osteoid. In contrast, the flattened bone-lining cells in the untreated diabetic rats showed minimal uptake (20 minutes) and secretion (4 hours) of labeled proline. In both MC and CMT-treated diabetic rats, the radioprecursor was localized in the osteoblasts and osteoid matrix in a pattern similar to that seen in the control rats at both 20 minutes and 4 hours after isotope injection. Labeling of the osteoid by the radioprecursor was greater as a result of CMT treatment than during minocycline treatment. These results suggest that the diabetes-induced suppression of synthesis and secretion of protein (presumably collagen and its precursor) by osteoblasts can be restored to near-normal levels by administration of tetracycline(s) and that this effect is mediated by a non-antimicrobial property of these antibiotics.