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Hypochlorous acid (HOCI), an ROS produced by neutrophils, has been shown to activate neutrophil procollagenase. The objective of the present study was to determine whether (1) HOCI also activated osteoblast procollagenase and (2) TCs inhibited this enzyme in the presence of HOCI. HOCI (5 \u03bcM) activated the proenzyme approximately sixfold (P &amp;lt; 0.01) from the medium of PTH-treated UMR-106\u201301 osteoblastic osteosarcoma cells as determined by functional collagenase assay (3H-methyl-labeled collagen substrate). Doxycycline (50\u2013400 \u03bcM) and chemically modified tetracycline, CMT-1 (100\u2013400 \u03bcM), significantly inhibited collagenase activity 50\u201390% and 40\u201380%, respectively, in the presence of 5 \u03bcM HOCI. Concentrations of 6\u201325 \u03bcM doxycycline and 10\u201350 \u03bcM CMT-1 had no significant effect. Furthermore, an excess concentration of cation (50 mM CaCI2 or 50 \u03bcM ZnCI2) added to the incubation mixtures containing either doxycycline or CMT-1 did not restore collagenase activity, as demonstrated by SDS-PAGE-fluorography. These data suggested that TCs reduced available HOCI and thus prevented the hypochlorous acid conversion of the osteoblast proenzyme to active collagenase. TCs may have therapeutic potential in the treatment of periodontitis and other diseases by several mechanisms that inhibit pathologic collagen breakdown.<\/jats:p>","DOI":"10.1002\/jbmr.5650081013","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T16:44:53Z","timestamp":1265215493000},"page":"1247-1253","source":"Crossref","is-referenced-by-count":77,"title":["Reactive oxygen species activate and tetracyclines inhibit rat osteoblast collagenase"],"prefix":"10.1093","volume":"8","author":[{"given":"Nungavaram S.","family":"Ramamurthy","sequence":"first","affiliation":[{"name":"State University of New York at Stony Brook, School of Dental Medicine, Department of Oral Biology and Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony T.","family":"Vernillo","sequence":"additional","affiliation":[{"name":"New York University, College of Dentistry, Division of Basic Sciences, Oral Medicine and Pathology Unit, New 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