{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T04:16:17Z","timestamp":1778991377926,"version":"3.51.4"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,1,26]],"date-time":"2005-01-26T00:00:00Z","timestamp":1106697600000},"content-version":"vor","delay-in-days":4896,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Anat. Rec."],"published-print":{"date-parts":[[1991,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteopenia is a recognized complication of diabetes mellitus in humans and experimental animals. We recently found that tetracyclines prevent osteopenia in the streptozotocin\u2010induced diabetic rat and that this effect was associated with a restoration of defective osteoblast morphology (Golub et al., 1990). The present study extends these initial ultrastructural observations by assessing osteoblast function in the untreated and tetracycline\u2010treated diabetic rats. After a 3\u2010week protocol, non\u2010diabetic control and diabetic rats, including those orally administered a tetracycline, minocycline (MC), or a non\u2010antimicrobial tetracycline analog (CMT), were perfusion\u2010fixed with an aldehyde mixture; the humeri were dissected and processed for ultracytochemical localization of alkaline phosphatase (ALPase) and Ca\u2010ATPase activities. Some rats from each experimental group received an intravenous injection of <jats:sup>3<\/jats:sup>H\u2010proline as a radioprecursor of procollagen, and the humeri were processed for light microscopic autoradiography. In addition, the osteoid volume in each experimental group was quantitatively examined by morphometric analysis of electron micrographs.<\/jats:p><jats:p>During the diabetic state, active cuboidal osteoblasts in the endosteum of control rats were replaced by flattened bone\u2010lining cells that contained few cytoplasmic organelles for protein synthesis (Golgi\u2010RER system), and active transport (mitochondria). Treating diabetic rats with MC, and even more so with CMT, appeared to \u201crestore\u201d osteoblast structure. During diabetes, bone\u2010lining cells incorporated little <jats:sup>3<\/jats:sup>H\u2010proline or secreted little labeled protein and produced only a very thin osteoid layer. Tetracycline administration to the diabetics increased both the incorporation of <jats:sup>3<\/jats:sup>H\u2010proline by osteoblasts and their secretion of labeled protein toward the osteoid matrix, in a pattern similar to that seen in the non\u2010diabetic controls. Intense alkaline phosphatase (ALPase) activity was cytochemically demonstrated along the plasma membranes of osteoblasts in the non\u2010diabetic control rats, but was completely absent from the bone\u2010lining cells in the diabetics. Similar to that described above, CMT therapy restored the ALPase activity in the diabetic osteoblasts and the effect of MC was less dramatic. The distribution and intensity of Ca\u2010ATPase in the osteoblast\u2010plasma membranes of the different groups of rats were similar to that of ALPase, except for the absence of detectable Ca\u2010ATPase in the MC\u2010treated diabetics. These results suggest that diabetes\u2010induced osteopenia reflects, al least in part, impaired osteoblast structure and function and that tetracyclines, by a non\u2010antimicrobial mechanism, may prevent this bone deficiency by normalizing these bone\u2010lining cells.<\/jats:p>","DOI":"10.1002\/ar.1092310105","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T20:37:35Z","timestamp":1109450255000},"page":"25-34","source":"Crossref","is-referenced-by-count":55,"title":["Tetracycline administration restores osteoblast structure and function during experimental diabetes"],"prefix":"10.1002","volume":"231","author":[{"given":"Takahisa","family":"Sasaki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruki","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nungavaram S.","family":"Ramamurthy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorne M.","family":"Golub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,1,26]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650030105"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1267\/ahc.14.705"},{"key":"e_1_2_1_4_1","unstructured":"Binz K. 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