title: Tetracycline administration increases collagen synthesis in osteoblasts of streptozotocin-induced diabetic rats: a quantitative autoradiographic study.
abstract: 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.
authors.affiliation: Second Department of Oral Anatomy, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sasaki
authors.forename: N S
authors.initials: NS
authors.lastname: Ramamurthy
authors.forename: L M
authors.initials: LM
authors.lastname: Golub
mesh_terms: D000818:Animals; D001345:Autoradiography; D003094:Collagen / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D010006:Osteoblasts / Q000378:metabolism* / Q000648:ultrastructure; D010024:Osteoporosis / Q000209:etiology; D011347:Procollagen / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin; D013752:Tetracycline / Q000494:pharmacology* / Q000627:therapeutic use; D014316:Tritium
chemical_list: D011347:Procollagen; D014316:Tritium; D013311:Streptozocin; D003094:Collagen; D011392:Proline; D013752:Tetracycline