{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:39:42Z","timestamp":1791085182917,"version":"4.1.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2021,4,10]],"date-time":"2021-04-10T00:00:00Z","timestamp":1618012800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R00DE028439 and R03DE029258"],"award-info":[{"award-number":["R00DE028439 and R03DE029258"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE12889"],"award-info":[{"award-number":["R01DE12889"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R03DE028411 and R01DE027639"],"award-info":[{"award-number":["R03DE028411 and R01DE027639"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["NIAMS Intramural Research Program"],"award-info":[{"award-number":["NIAMS Intramural Research Program"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS Research Fellowship for Japanese Biomedical a"],"award-info":[{"award-number":["JSPS Research Fellowship for Japanese Biomedical a"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>\n                    Factors regulating the ratio of pyrophosphate (PP\n                    <jats:sub>i<\/jats:sub>\n                    ) to phosphate (P\n                    <jats:sub>i<\/jats:sub>\n                    ) modulate biomineralization. Tissue-nonspecific alkaline phosphatase (TNAP) is a key promineralization enzyme that hydrolyzes the potent mineralization inhibitor PP\n                    <jats:sub>i<\/jats:sub>\n                    . The goal of this study was to determine whether TNAP could promote periodontal regeneration in bone sialoprotein knockout mice ( Ibsp\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice), which are known to have a periodontal disease phenotype. Delivery of TNAP was accomplished either systemically (through a lentiviral construct expressing a mineral-targeted TNAP-D\n                    <jats:sub>10<\/jats:sub>\n                    protein) or locally (through addition of recombinant human TNAP to a fenestration defect model). Systemic TNAP-D\n                    <jats:sub>10<\/jats:sub>\n                    delivered by intramuscular injection at 5\u2009d postnatal (dpn) increased circulating alkaline phosphatase (ALP) levels in Ibsp\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice by 5-fold at 30\u2009dpn, with levels returning to normal by 60\u2009dpn when tissues were evaluated by micro\u2013computed tomography and histology. Local delivery of recombinant human TNAP to fenestration defects in 5-wk-old wild type (WT) and Ibsp\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice did not alter long-term circulating ALP levels, and tissues were evaluated by micro\u2013computed tomography and histology at postoperative day 45. Systemic and local delivery of TNAP significantly increased alveolar bone volume (20% and 37%, respectively) and cementum thickness (3- and 42-fold) in Ibsp\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, with evidence for periodontal ligament attachment and bone\/cementum marker localization. Local delivery significantly increased regenerated cementum and bone in WT mice. Addition of 100-\u03bcg\/mL bovine intestinal ALP to culture media to increase ALP in vitro increased media P\n                    <jats:sub>i<\/jats:sub>\n                    concentration, mineralization, and Spp1 and Dmp1 marker gene expression in WT and Ibsp\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    OCCM.30 cementoblasts. Use of phosphonoformic acid, a nonspecific inhibitor of sodium P\n                    <jats:sub>i<\/jats:sub>\n                    cotransport, indicated that effects of bovine intestinal ALP on mineralization and marker gene expression were in part through P\n                    <jats:sub>i<\/jats:sub>\n                    transport. These findings show for the first time through multiple in vivo and in vitro approaches that pharmacologic modulation of P\n                    <jats:sub>i<\/jats:sub>\n                    \/PP\n                    <jats:sub>i<\/jats:sub>\n                    metabolism can overcome periodontal breakdown and accomplish regeneration.\n                  <\/jats:p>","DOI":"10.1177\/00220345211005677","type":"journal-article","created":{"date-parts":[[2021,4,10]],"date-time":"2021-04-10T04:56:30Z","timestamp":1618030590000},"page":"993-1001","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Delivery of Alkaline Phosphatase Promotes Periodontal Regeneration in Mice"],"prefix":"10.1177","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7655-9658","authenticated-orcid":false,"given":"A.","family":"Nagasaki","sequence":"first","affiliation":[{"name":"Laboratory of Oral Connective Tissue Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Nagasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Connective Tissue Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.D.","family":"Kear","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Connective Tissue Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.D.","family":"Tadesse","sequence":"additional","affiliation":[{"name":"Laboratory of Oral Connective Tissue Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes 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