{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:12:41Z","timestamp":1778634761713,"version":"3.51.4"},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,1,1]],"date-time":"2002-01-01T00:00:00Z","timestamp":1009843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Tetracyclines, particularly doxycycline (Doxy), and their nonantimicrobial chemically\u2010modified derivatives (CMTs) inhibit the activities of human matrix metalloproteinases (MMPs), and reduce the severity and progression of periodontal disease in animal models and humans. In this study, the effects of Doxy and CMT\u20101, \u20103, and \u20105 on proteolytic, serpinolytic, and progelatinase\u2010B activation activities of potent periodontopathogens were studied.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The effect of Doxy and CMTs (0.5 to 50 \u03bcM) on proteolytic activities were investigated by incubating bacteria with chromogenic substrates or human serum albumin. A collagenolytic fraction of <jats:italic>Porphyromonas gingivalis<\/jats:italic> was used to evaluate the effect of these substances on collagenolytic (type I collagen) and serpinolytic (\u03b11\u2010proteinase inhibitor) activities. Lastly, the effect of Doxy on progelatinase\u2010B (pro\u2010MMP\u20109) activation by purified proteinases from <jats:italic>P. gingivalis<\/jats:italic> and <jats:italic>Treponema denticola<\/jats:italic> was investigated by SDS\u2010PAGE\/Western immunoblotting.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Doxy and CMTs, except CMT\u20105 which lacks the structural elements required for cation chelation, inhibited Arg\u2010 and Lys\u2010gingipain activities as well as collagenolytic activity of <jats:italic>P. gingivalis<\/jats:italic>. Doxy and CMTs did not markedly affect the chymotrypsin\u2010like activity of <jats:italic>T. denticola<\/jats:italic> but inhibited its trypsin\u2010like activity. In addition, degradation of human serum albumin by cells of <jats:italic>P. gingivalis<\/jats:italic> and <jats:italic>T. denticola<\/jats:italic> was strongly inhibited by Doxy and CMT\u20101. Doxy and CMT\u20101 also inhibited the inactivation of \u03b11\u2010proteinase inhibitor (serpinolytic activity) by a collagenolytic fraction of <jats:italic>P. gingivalis<\/jats:italic>. Lastly, Doxy prevented the latent to active conversion of human neutrophil progelatinase\u2010B (pro\u2010MMP\u20109) by Arg\u2010gingipains A\/B of <jats:italic>P. gingivalis<\/jats:italic> but not by the chymotrypsin\u2010like proteinase of <jats:italic>T. denticola<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Data from this study suggest that Doxy and CMTs have the potential to inhibit the periodontopathogenic bacterial proteinases, which contribute to tissue destruction cascades during periodontitis directly and indirectly by triggering the host response. <jats:italic>J Periodontol 2002;73:79\u201085.<\/jats:italic><\/jats:p>","DOI":"10.1902\/jop.2002.73.1.79","type":"journal-article","created":{"date-parts":[[2005,2,2]],"date-time":"2005-02-02T07:05:08Z","timestamp":1107327908000},"page":"79-85","source":"Crossref","is-referenced-by-count":42,"title":["Inhibition of Proteolytic, Serpinolytic, and Progelatinase\u2010B Activation Activities of Periodontopathogens by Doxycycline and the Non\u2010Antimicrobial Chemically Modified Tetracycline Derivatives"],"prefix":"10.1002","volume":"73","author":[{"given":"D.","family":"Grenier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Plamondon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Sorsa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u2010M.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"McNamara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.S","family":"Ramamurthy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.M.","family":"Golub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.","family":"Teronen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Mayrand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,1]]},"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1902\/jop.2002.73.1.79","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T14:37:06Z","timestamp":1760884626000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1902\/jop.2002.73.1.79"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,1]]}},"alternative-id":["10.1902\/jop.2002.73.1.79"],"URL":"https:\/\/doi.org\/10.1902\/jop.2002.73.1.79","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"value":"0022-3492","type":"print"},{"value":"1943-3670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,1]]}}}