{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:37:27Z","timestamp":1786977447754,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670993 and 81873716"],"award-info":[{"award-number":["81670993 and 81873716"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Periodontitis is one of the main causes of tooth loss and has been confirmed as the sixth complication of diabetes. Metformin promotes the osteogenic differentiation of stem cells. Periodontal ligament stem cells (PDLSCs) are the best candidate stem cells for periodontal tissue regeneration. Herein, we aimed to identify the effects of metformin on the proliferation, migration, and osteogenic differentiation of PDLSCs in vitro. PDLSCs were isolated by limiting dilution, and their characteristics were assessed by colony formation assay and flow cytometry. Cell counting and migration assays were used to investigate the effects of metformin on proliferation and migration. The osteogenic differentiation ability of PDLSCs was detected by alkaline phosphatase (ALP) activity and Alizarin Red S staining. Gene and protein levels of osteogenesis\u2010related markers were determined by quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR) and western blot analysis, respectively. Metformin treatment at 10\u2009\u03bcM did not affect PDLSC proliferation, while at 50 and 100\u2009\u03bcM, metformin time\u2010dependently enhanced PDLSC proliferation and significantly increased cell numbers after 5 and 7 days of stimulation (\n                    <jats:italic>P\u2009<\/jats:italic>\n                    &lt;\n\u20090.05). In addition, 50\u2009\u03bcM metformin exhibited a maximal effect on migration, ALP activity, and mineral deposition (\n                    <jats:italic>P\u2009<\/jats:italic>\n                    &lt;\n\u20090.05). Furthermore, 50\u2009\u03bcM metformin significantly upregulated the gene expression levels of\n                    <jats:italic>ALP<\/jats:italic>\n                    ,\n                    <jats:italic>BSP<\/jats:italic>\n                    ,\n                    <jats:italic>OPN<\/jats:italic>\n                    ,\n                    <jats:italic>OCN<\/jats:italic>\n                    , and\n                    <jats:italic>Runx2<\/jats:italic>\n                    and the protein expression of ALP and Runx2 (\n                    <jats:italic>P\u2009<\/jats:italic>\n                    &lt;\n\u20090.05). In summary, our study confirms that metformin facilitates the proliferation, migration, and osteogenic differentiation of PDLSCs in vitro and could be used as a new strategy for periodontal tissue regeneration.\n                  <\/jats:p>","DOI":"10.1002\/cbin.11202","type":"journal-article","created":{"date-parts":[[2019,7,11]],"date-time":"2019-07-11T02:06:30Z","timestamp":1562810790000},"page":"70-79","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Metformin facilitates the proliferation, migration, and osteogenic differentiation of periodontal ligament stem cells in vitro"],"prefix":"10.1002","volume":"44","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Periodontology, School and Hospital of Stomatology Shandong University &amp; Shandong Provincial Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration  No. 44\u20101 Wenhua Road West Jinan 250012 China"},{"name":"Department of Endodontics, Hospital of stomatology Zunyi medical University  No. 149 Dalian Road Zunyi 563000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School and Hospital of Stomatology Shandong University &amp; Shandong Provincial Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration  No. 44\u20101 Wenhua Road West Jinan 250012 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School and Hospital of Stomatology Shandong University &amp; Shandong Provincial Key Laboratory of Oral Tissue Regeneration &amp; Shandong Engineering Laboratory for Dental Materials and Oral Tissue 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