{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:23:22Z","timestamp":1791905002741,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,11,8]],"date-time":"2013-11-08T00:00:00Z","timestamp":1383868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Periodontal ligament stem cells (<jats:styled-content style=\"fixed-case\">PDLSC<\/jats:styled-content>s) are considered as potential mesenchymal stem cell sources for future clinical applications in periodontal regeneration therapy. Simvastation, widely used for lowering serum cholesterol, is known to have a bone stimulatory effect. However, it is not clear whether simvastation affects the differentiation of <jats:styled-content style=\"fixed-case\">PDLSC<\/jats:styled-content>s. This study examined the effects of simvastatin on human <jats:styled-content style=\"fixed-case\">PDLSC<\/jats:styled-content>s in vitro and in vivo. Using the limiting dilution technique, human <jats:styled-content style=\"fixed-case\">PDLSC<\/jats:styled-content>s were isolated and expanded. <jats:styled-content style=\"fixed-case\">PDLSC<\/jats:styled-content>s were cultured with simvastatin (0.01\u201310\u00a0\u03bc<jats:sc>m<\/jats:sc>), and the proliferation was measured. The osteogenic differentiation was characterized by alkaline phosphatase (<jats:styled-content style=\"fixed-case\">ALP<\/jats:styled-content>) activity and Alizarin Red\u2010S staining for calcium deposition. The gene expression levels of osteogenic markers were evaluated by <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. In addition, <jats:styled-content style=\"fixed-case\">PDLSC<\/jats:styled-content>s were transplanted into nude mice with ceramic bovine bone powders as carriers to observe the capacity of mineralized tissue formation in vivo. Simvastatin at concentrations &lt;1\u00a0\u03bc<jats:sc>m<\/jats:sc> did not suppress the proliferation of <jats:styled-content style=\"fixed-case\">PDLSC<\/jats:styled-content>s. After the administration of 0.1\u00a0\u03bc<jats:sc>m<\/jats:sc> simvastatin, the expression of <jats:styled-content style=\"fixed-case\">ALP<\/jats:styled-content>, bone sialoprotein, and bone morphogenetic protein\u20102 genes were significantly upregulated, and the <jats:styled-content style=\"fixed-case\">ALP<\/jats:styled-content> activity and mineralized nodule formation were significantly higher in the simvastatin\u2010treated cells than the control cells. In addition, the in vivo transplantation results showed that simvastatin treatment promoted the degree of mineralized tissue formation. Collectively, simvastatin has positive effects on osteogenic differentiation of human <jats:styled-content style=\"fixed-case\">PDLSC<\/jats:styled-content>s in vitro and in vivo. This suggests that simvastatin might be a useful osteogenic induction agent for periodontal bone regeneration.<\/jats:p>","DOI":"10.1111\/fcp.12050","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T22:30:36Z","timestamp":1381530636000},"page":"583-592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Simvastatin induces the osteogenic differentiation of human periodontal ligament stem cells"],"prefix":"10.1111","volume":"28","author":[{"given":"Bing\u2010jiao","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Orthodontics School of Stomatology Tongji University 399 YanChangZhong Road Shanghai 200072 China"},{"name":"Department of Orthodontics Shanghai Stomatological Disease Center 1258 FuXingZhong Road Shanghai 200002 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue\u2010hua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthodontics School of Stomatology Tongji University 399 YanChangZhong Road Shanghai 200072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2009.01593.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16627-0"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2012.02.017"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2010.01597.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.04.071"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2009.080568"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-012-1392-x"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2004.00541.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2012.120339"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2008.11.024"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.2010.00870.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5446.1946"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2010.03.004"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2010.03.003"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2009.11.021"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.163"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-011-0327-0"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12006"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2011.12.025"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2007.01024.x"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2012.120114"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2010.01329.x"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13577-011-0028-x"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2005.76.2.295"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2008.01106.x"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.05.025"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-11-18"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910208100806"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.4.696"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.06.032"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1159\/000127448"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(01)00606-8"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606706200"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2009.090429"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2007.0288"}],"container-title":["Fundamental &amp; 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