{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:32:23Z","timestamp":1790382743682,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR062680"],"award-info":[{"award-number":["R01 AR062680"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Local application of statins has shown potential in preventing and regenerating bone loss associated with experimental periodontitis. This study evaluates the effect of a novel simvastatin (SIM) prodrug (capable of delivering high doses to periodontitis inflammatory lesion and cells) on experimental periodontitis bone loss and inflammation.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Forty mature female Sprague Dawley rats were subjected to ligature\u2010induced experimental periodontitis between maxillary first and second molars (M1\u2010M2). Equal groups were treated with three weekly doses of: 1) prodrug carrier alone (mPEG); 2) 0.5 mg SIM dose equivalent in carrier (SIM\/SIM\u2010mPEG); 3) 1.0 mg SIM\/SIM\u2010mPEG; 4) 1.5 mg SIM\/SIM\u2010mPEG; or 5) ligature alone. Contralateral molars served as unmanipulated controls. Four weeks after initiation of periodontitis, animals were euthanized, the M1\u2010M2 interproximal was evaluated with microcomputed tomography and histology, and data were analyzed with one\u2010way analysis of variance.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Ligature alone caused a mean bone loss of 1.01 \u00b1 0.06 mm from the cemento\u2010enamel junction, whereas all doses of SIM\/SIM\u2010mPEG reduced bone loss, especially 1.5 mg SIM\/SIM\u2010mPEG (0.68 \u00b1 0.05 mm, <jats:italic>P<\/jats:italic> &lt;0.001), which was not statistically different from contralateral control (0.47 \u00b1 0.06 mm). A dose of 1.5 mg SIM\/SIM\u2010mPEG also reduced percentage of neutrophils compared with carrier alone (2.0% \u00b1 1.0% versus 5.7% \u00b1 1.1%; <jats:italic>P<\/jats:italic> &lt;0.05), and increased amount of uninflamed connective tissue in the M1\u2010M2 interproximal area (65.2% \u00b1 3.3% versus 46.3% \u00b1 3.3%; <jats:italic>P<\/jats:italic> &lt;0.001). The mPEG carrier alone did not have bone\u2010sparing or anti\u2010inflammatory properties.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Multiple local 1.5\u2010mg doses of a macromolecular SIM prodrug decreases amount of experimental periodontitis bone loss and inflammation in rats.<\/jats:p>","DOI":"10.1902\/jop.2016.150599","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T12:30:22Z","timestamp":1453465822000},"page":"577-582","source":"Crossref","is-referenced-by-count":24,"title":["Effect of Simvastatin Prodrug on Experimental Periodontitis"],"prefix":"10.1002","volume":"87","author":[{"given":"Aaron D.","family":"Bradley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenshan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pranke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian J.","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Reinhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612013397762"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2012.01.012"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/gme.0b013e3181d3e036"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2014.12.028"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2007.12.045"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2007.060480"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-014-0284-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2007.01024.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12036"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2012.120114"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0722.2000.00766.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2005.76.11.1901"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2013.12.009"}],"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1902\/jop.2016.150599","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T12:52:00Z","timestamp":1760878320000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1902\/jop.2016.150599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5]]},"references-count":13,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1902\/jop.2016.150599"],"URL":"https:\/\/doi.org\/10.1902\/jop.2016.150599","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"value":"0022-3492","type":"print"},{"value":"1943-3670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5]]}}}