{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:41:49Z","timestamp":1791276109735,"version":"4.1.0"},"reference-count":33,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2011,1,6]],"date-time":"2011-01-06T00:00:00Z","timestamp":1294272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:p>\n                    Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice ( Akp2\n                    <jats:sup>-\/-<\/jats:sup>\n                    ) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B\n                    <jats:sub>6<\/jats:sub>\n                    -responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD\n                    <jats:sub>10<\/jats:sub>\n                    ). sALP-FcD\n                    <jats:sub>10<\/jats:sub>\n                    prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin \u2013 a marker of acellular cementum \u2013 was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life \u2013 where the majority of tooth root development occurs, including acellular cementum formation \u2013 could prevent the accelerated tooth loss seen in individuals with HPP.\n                  <\/jats:p>","DOI":"10.1177\/0022034510393517","type":"journal-article","created":{"date-parts":[[2011,1,6]],"date-time":"2011-01-06T23:40:41Z","timestamp":1294357241000},"page":"470-476","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":120,"title":["Enzyme Replacement Therapy Prevents Dental Defects in a Model of Hypophosphatasia"],"prefix":"10.1177","volume":"90","author":[{"given":"M.D.","family":"McKee","sequence":"first","affiliation":[{"name":"Faculty of Dentistry, and Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Strathcona Anatomy and Dentistry Bldg., 3640 University Street, Montreal, Quebec, Canada H3A 2B2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Nakano","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, and Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Strathcona Anatomy and Dentistry Bldg., 3640 University Street, Montreal, Quebec, Canada H3A 2B2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.L.","family":"Masica","sequence":"additional","affiliation":[{"name":"Program in Molecular Biophysics, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.J.","family":"Gray","sequence":"additional","affiliation":[{"name":"Program in Molecular Biophysics, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 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