{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T14:03:26Z","timestamp":1773065006648,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T00:00:00Z","timestamp":1542672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004083","name":"Ministry of Science ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF\u2010 2017R1A2B4004618"],"award-info":[{"award-number":["NRF\u2010 2017R1A2B4004618"]}],"id":[{"id":"10.13039\/501100004083","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004083","name":"Ministry of Science ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF\u20102017R1A5A2015391"],"award-info":[{"award-number":["NRF\u20102017R1A5A2015391"]}],"id":[{"id":"10.13039\/501100004083","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Periodontitis is not only one of the most prevalent inflammatory diseases among adults, but also commonly linked to numerous systemic conditions including cardiovascular diseases, stroke, and diabetes. Although osteoclasts are responsible for the alveolar bone resorption during periodontitis pathogenesis, the development of pharmacologic strategies targeting these cells has not been vastly fruitful.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Bone marrow macrophages were cultured in the presence of macrophage\u2010colony stimulating factor (M\u2010CSF) and receptor activator of nuclear factor \u03baB ligand (RANKL) to examine the direct effect of acalabrutinib on osteoclastogenesis. Ca<jats:sup>2+<\/jats:sup> oscillation and nuclear localization of NFATc1 in osteoclast precursors were examined to determine the precise molecular mechanism. LPS\u2010induced alveolar bone loss model was employed for studying effect in <jats:italic>in vivo<\/jats:italic> bone resorption.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Acalabrutinib directly inhibited RANKL and LPS\u2010induced <jats:italic>in vitro<\/jats:italic> osteoclast differentiation. In addition, acalabrutinib inhibited RANKL\u2010induced phosphorylation of mitogen\u2010activated protein kinases and reduced the expression of NF\u2010\u03baB. The inhibitory mechanism involved suppression of Ca<jats:sup>2+<\/jats:sup> oscillation in osteoclast precursors resulting in the decreased NFATc1 expression and nuclear localization, which is a crucial prerequisite for osteoclastogenesis. The administration of acalabrutinib significantly reduced <jats:italic>P.\u00a0gingivalis<\/jats:italic> lipopolysaccharide\u2010induced alveolar bone erosion in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data indicate that acalabrutinib is an effective inhibitor of osteoclastogenesis both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, with a potential for a novel strategy against bone destruction by periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jper.18-0334","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T05:40:18Z","timestamp":1541137218000},"page":"546-554","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A novel Bruton's tyrosine kinase inhibitor, acalabrutinib, suppresses osteoclast differentiation and <i>Porphyromonas gingivalis<\/i> lipopolysaccharide\u2010induced alveolar bone resorption"],"prefix":"10.1002","volume":"90","author":[{"given":"Nitin Kumar","family":"Pokhrel","sequence":"first","affiliation":[{"name":"Department of Biochemistry School of Dentistry Kyungpook National University  Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong\u2010Gun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Periodontology School of Dentistry Kyungpook National University  Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyo Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Dentistry Kyungpook National University  Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyung Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oral Physiology School of Dentistry &amp; Institute of Translational Dental Science Pusan National University  Yangsan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Hye","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology School of Dentistry &amp; Institute of Translational Dental Science Pusan National University  Yangsan Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So\u2010Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery School of Dentistry Kyungpook National University  Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae\u2010Geon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery School of Dentistry Kyungpook National University  Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heon\u2010Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology School of Dentistry Kyungpook National University  Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae\u2010Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Dentistry Kyungpook National University  Daegu Korea"},{"name":"Institute for Hard Tissue and Bio\u2010tooth Regeneration (IHBR) School of Dentistry Kyungpook National University  Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngkyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Dentistry Kyungpook National University  Daegu Korea"},{"name":"Institute for Hard Tissue and Bio\u2010tooth Regeneration (IHBR) School of Dentistry Kyungpook National University  Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1504"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00695-8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.09.023"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1593"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1508"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200011)43:11<2523::AID-ANR20>3.0.CO;2-Z"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2010.00347.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00741.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8332900"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90667-F"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/361226a0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.121"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0779-z"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.09.011"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0513307"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01454"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708935200"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.11.025"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000412"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1561"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17030422"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1805"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.037"},{"key":"e_1_2_9_26_1","first-page":"945","article-title":"Bruton's tyrosine kinase is involved in innate and adaptive immunity","volume":"20","author":"Brunner C","year":"2005","journal-title":"Histol Histopathol"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.03.028"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-11-317016"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-016-0250-9"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515572021"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2405"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051150"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00821.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00369-6"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.10.1735"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.7.1297"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181782"}],"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2FJPER.18-0334","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JPER.18-0334","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/JPER.18-0334","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JPER.18-0334","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T12:37:10Z","timestamp":1760877430000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1002\/JPER.18-0334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,20]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/JPER.18-0334"],"URL":"https:\/\/doi.org\/10.1002\/jper.18-0334","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"value":"0022-3492","type":"print"},{"value":"1943-3670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,20]]},"assertion":[{"value":"2018-05-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}