{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:39:32Z","timestamp":1762101572410},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,6,20]],"date-time":"2014-06-20T00:00:00Z","timestamp":1403222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Grants-in-Aid for Scientific Research","award":["25862045","23249086"],"award-info":[{"award-number":["25862045","23249086"]}]},{"name":"Japan China Sasakawa Medical Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>The proteasome inhibitor, bortezomib, is known to induce osteoblastic differentiation in a number of cell lines, such as mesenchymal stem cells and osteoblastic precursor cells. As periodontal ligament (<jats:styled-content style=\"fixed-case\">PDL<\/jats:styled-content>) cells are multipotent, we examined whether bortezomib may induce the differentiation of <jats:styled-content style=\"fixed-case\">PDL<\/jats:styled-content> cells into hard\u2010tissue\u2010forming cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and Methods<\/jats:title><jats:p>A mouse <jats:styled-content style=\"fixed-case\">PDL<\/jats:styled-content> clone cell line, <jats:styled-content style=\"fixed-case\">MPDL<\/jats:styled-content>22 cells, was cultured in mineralization medium in the presence or absence of bortezomib. Expression of calcification\u2010related genes and calcified\u2010nodule formation were evaluated by real\u2010time PCR and Alizarin Red staining, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bortezomib increased the expression of calcification\u2010related mRNAs, such as tissue nonspecific alkaline phosphatase isoenzyme (<jats:italic>ALPase<\/jats:italic>), bone sialoprotein (<jats:italic>Bsp<\/jats:italic>), runt\u2010related transcription factor 2 (<jats:italic>Runx2<\/jats:italic>) and osteopontin, and calcified\u2010nodule formation in MPDL22 cells. These effects were induced, in part, by increasing the cytosolic accumulation and nuclear translocation of \u03b2\u2010catenin, leading to an increase in expression of bone morphogenetic protein (<jats:italic>Bmp<\/jats:italic>)<jats:italic>\u20102<\/jats:italic>,<jats:italic> \u20104<\/jats:italic> and <jats:italic>\u20106<\/jats:italic> mRNAs. In addition, bortezomib enhanced BMP\u20102\u2010induced expression of <jats:italic>Bsp<\/jats:italic> and osteopontin mRNAs and increased calcified\u2010nodule formation in MPDL22 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Bortezomib induced cytodifferentiation and mineralization of PDL cells by enhancing the accumulation of \u03b2\u2010catenin within the cytosol and the nucleus and increasing the expression of <jats:italic>Bmp\u20102, \u20104<\/jats:italic> and <jats:italic>\u20106<\/jats:italic> mRNAs. Moreover, bortezomib enhanced the BMP\u20102\u2010induced cytodifferentiation and mineralization of PDL cells, suggesting that bortezomib may be efficacious for use in periodontal regeneration therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12202","type":"journal-article","created":{"date-parts":[[2014,6,20]],"date-time":"2014-06-20T11:50:39Z","timestamp":1403265039000},"page":"248-255","source":"Crossref","is-referenced-by-count":12,"title":["Effects of the proteasome inhibitor, bortezomib, on cytodifferentiation and mineralization of periodontal ligament cells"],"prefix":"10.1111","volume":"50","author":[{"given":"J.","family":"Kitagaki","sequence":"first","affiliation":[{"name":"Department of Periodontology Division of Oral Biology and Disease Control Osaka University Graduate School of Dentistry Suita Osaka Japan"},{"name":"Challenge to Intractable Oral Diseases Center for Translational Dental Research Osaka University Dental Hospital Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Miyauchi","sequence":"additional","affiliation":[{"name":"Department of Periodontology Division of Oral Biology and Disease Control Osaka University Graduate School of Dentistry Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. J","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Periodontology Division of Oral Biology and Disease Control Osaka University Graduate School of Dentistry Suita Osaka Japan"},{"name":"Department of Periodontology Stomatology Hospital of Guangdong Province Southern Medical University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Periodontology Division of Oral Biology and Disease Control Osaka University Graduate School of Dentistry Suita Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Periodontology Division of Oral Biology and Disease Control Osaka University Graduate School of Dentistry Suita Osaka 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