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However, bone remodeling requires the activity of osteoclasts as well as osteoblasts. To determine the in vivo effects of tetracycline on osteoclasts in long bones, either a tetracycline (minocycline, TC) or its chemically modified non\u2010antibiotic analogue (CMT), 4\u2010de\u2010dimethylaminotetracycline, was administrated daily to streptozotocin\u2010induced diabetic rats by oral intubation. After 21 days, the rats were perfusion\u2010fixed with a mixture of formaldehyde and glutaraldehyde, and the humeri were dissected and processed for ultracytochemical demonstration of acid trimetaphosphatase (ACPase) activity. In untreated non\u2010diabetic (control) rats, the osteoclasts at the zone of provisional ossification exhibited abundant mitochondria and cisterns of rough endoplasmic reticulum (RER) throughout the cytoplasm, prominent stacks of Golgi membranes, and lysosomes in the perinuclear cytoplasm, and numerous various pale vacuoles in the cytoplasmic area adjacent to well\u2010developed ruffled border. Intense ACPase activity was observed in the Golgi saccules, lysosomes, pale vacuoles, and the extracellular canals of ruffled border. The reaction products were also noted along the resorbing bone surfaces associated with the osteoclast ruffled border. The osteoclasts in the untreated diabetic rats showed a cytoplasmic organization similar to that of the non\u2010diabetic control rats, but showed little or no ruffled border which was replaced by a broad clear zone in some of these cells. However, most of the osteoclasts on bone matrix in the diabetics were devoid of both a ruffled border and a clear zone. ACPase activity was detected in the osteoclast cytoplasm of diabetic rat, as in the controls, but to a much lesser extent along the broad clear zone facing the resorbing bone surfaces. The osteoclasts in TC\u2010treated diabetic rats possessed both a clear zone and a small ruffled border. However, in some cases, they lacked both structures reminiscent of the untreated diabetic cells. The osteoclasts of CMT\u2010treated diabetic rats exhibited structural and enzymatic features essentially identical to those of the non\u2010diabetic control rats. These results suggest that the diabetes\u2010induced osteopenia results, at least in part, from degeneration of osteoclasts (as well as atrophic osteoblasts) and that tetracyclines may be effective in preventing these abnormalities by a mechanism not dependent on the drugs' antimicrobial properties.<\/jats:p>","DOI":"10.1002\/ar.1092270406","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T20:46:54Z","timestamp":1109450814000},"page":"427-436","source":"Crossref","is-referenced-by-count":27,"title":["Tetracycline administration normalizes the structure and acid phosphatase activity of osteoclasts in streptozotocin\u2010induced diabetic rats"],"prefix":"10.1002","volume":"227","author":[{"given":"Haruki","family":"Kaneko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahisa","family":"Sasaki","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","unstructured":"Bain S. 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