{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T12:49:05Z","timestamp":1777812545273,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2017,12,15]],"date-time":"2017-12-15T00:00:00Z","timestamp":1513296000000},"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":[[2018,4]]},"abstract":"<jats:p>\n                    Mineralization of bones and teeth is tightly regulated by levels of extracellular inorganic phosphate (P\n                    <jats:sub>i<\/jats:sub>\n                    ) and pyrophosphate (PP\n                    <jats:sub>i<\/jats:sub>\n                    ). Three regulators that control pericellular concentrations of P\n                    <jats:sub>i<\/jats:sub>\n                    and PP\n                    <jats:sub>i<\/jats:sub>\n                    include tissue-nonspecific alkaline phosphatase (TNAP), progressive ankylosis protein (ANK), and ectonucleotide pyrophosphatase\/phosphodiesterase 1 (ENPP1). Inactivation of these factors results in mineralization disorders affecting teeth and their supporting structures. This study for the first time analyzed the effect of decreased PP\n                    <jats:sub>i<\/jats:sub>\n                    on dental development in individuals with generalized arterial calcification of infancy (GACI) due to loss-of-function mutations in the ENPP1 gene. Four of the 5 subjects reported a history of infraocclusion, overretained primary teeth, ankylosis, and\/or slow orthodontic tooth movement, suggesting altered mineral metabolism contributing to disrupted tooth movement and exfoliation. All subjects had radiographic evidence of unusually protruding cervical root morphology in primary and\/or secondary dentitions. High-resolution micro\u2013computed tomography (micro-CT) analyses of extracted primary teeth from 3 GACI subjects revealed 4-fold increased cervical cementum thickness ( P = 0.00007) and a 23% increase in cementum density ( P = 0.009) compared to age-matched healthy control teeth. There were no differences in enamel and dentin densities between GACI and control teeth. Histology revealed dramatically expanded cervical cementum in GACI teeth, including cementocyte-like cells and unusual patterns of cementum resorption and repair. Micro-CT analysis of Enpp1 mutant mouse molars revealed 4-fold increased acellular cementum thickness ( P = 0.002) and 5-fold increased cementum volume ( P = 0.002), with no changes in enamel or dentin. Immunohistochemistry identified elevated ENPP1 expression in cementoblasts of human and mouse control teeth. Collectively, these findings reveal a novel dental phenotype in GACI and identify ENPP1 genetic mutations associated with hypercementosis. The sensitivity of cementum to reduced PP\n                    <jats:sub>i<\/jats:sub>\n                    levels in both human and mouse teeth establishes this as a well-conserved and fundamental biological process directing cementogenesis across species (ClinicalTrials.gov NCT00369421).\n                  <\/jats:p>","DOI":"10.1177\/0022034517744773","type":"journal-article","created":{"date-parts":[[2017,12,16]],"date-time":"2017-12-16T02:30:44Z","timestamp":1513391444000},"page":"432-441","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":58,"title":["Hypercementosis Associated with\n                    <i>ENPP1<\/i>\n                    Mutations and GACI"],"prefix":"10.1177","volume":"97","author":[{"given":"V.","family":"Thumbigere-Math","sequence":"first","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA"},{"name":"Division of Periodontics, School of Dentistry, University of Maryland, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Alqadi","sequence":"additional","affiliation":[{"name":"Division of Public and Child Dental Health, Dublin Dental University Hospital, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.I.","family":"Chalmers","sequence":"additional","affiliation":[{"name":"Analytics and Publication, DentaQuest Institute, Westborough, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.B.","family":"Chavez","sequence":"additional","affiliation":[{"name":"Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.Y.","family":"Chu","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.T.","family":"Collins","sequence":"additional","affiliation":[{"name":"Section on Skeletal Disorders and Mineral Homeostasis, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.R.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, USA"},{"name":"Division of Genetics and Metabolism, Children\u2019s National Health System, Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"FitzGerald","sequence":"additional","affiliation":[{"name":"Division of Public and Child Dental Health, Dublin Dental University Hospital, Dublin, Ireland"},{"name":"Our Lady\u2019s Children\u2019s Hospital, Crumlin, Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.I.","family":"Gafni","sequence":"additional","affiliation":[{"name":"Section on Skeletal Disorders and Mineral Homeostasis, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.A.","family":"Gahl","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.S.","family":"Hsu","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.S.","family":"Ramnitz","sequence":"additional","affiliation":[{"name":"Section on Skeletal Disorders and Mineral Homeostasis, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.J.","family":"Somerman","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.G.","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.L.","family":"Foster","sequence":"additional","affiliation":[{"name":"Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2017,12,15]]},"reference":[{"key":"bibr1-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62481-9"},{"key":"bibr2-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001740107"},{"key":"bibr3-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516677528"},{"key":"bibr4-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-007-0499-y"},{"key":"bibr5-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514529304"},{"key":"bibr6-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-0733"},{"key":"bibr7-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-011-1572-9"},{"key":"bibr8-0022034517744773","volume-title":"Genereviews(r)","author":"Ferreira C","year":"2014"},{"key":"bibr9-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37574"},{"key":"bibr10-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1038\/ijos.2012.57"},{"key":"bibr11-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516663633"},{"key":"bibr12-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038393"},{"key":"bibr13-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1210\/er.2013-1009"},{"key":"bibr14-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514529150"},{"key":"bibr15-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1002\/9781118704868.ch20"},{"key":"bibr16-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1177\/00220345980770011201"},{"key":"bibr17-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.09.016"},{"key":"bibr18-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63208-7"},{"key":"bibr19-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-010-9366-z"},{"issue":"3","key":"bibr20-0022034517744773","first-page":"179","volume":"36","author":"Humerfelt A","year":"1966","journal-title":"Angle Orthod"},{"key":"bibr21-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjoms.2012.05.008"},{"key":"bibr22-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0722.2008.00529.x"},{"key":"bibr23-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.010"},{"key":"bibr24-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.012765"},{"key":"bibr25-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2012.10811.x"},{"key":"bibr26-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.006"},{"key":"bibr27-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032177"},{"issue":"4","key":"bibr28-0022034517744773","first-page":"192","volume":"60","author":"McGeown M","year":"2014","journal-title":"J Ir Dent Assoc"},{"key":"bibr29-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-012-9672-8"},{"key":"bibr30-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1038\/bdj.2007.1063"},{"key":"bibr31-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1177\/154405910208101204"},{"key":"bibr32-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.01.010"},{"key":"bibr33-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1752"},{"key":"bibr34-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-6"},{"key":"bibr35-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.108.797704"},{"key":"bibr36-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1038\/ng1221"},{"key":"bibr37-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2016.01.015"},{"key":"bibr38-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2005.08.005"},{"key":"bibr39-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.14"},{"key":"bibr40-0022034517744773","doi-asserted-by":"publisher","DOI":"10.1038\/ijos.2014.62"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0022034517744773","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0022034517744773","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0022034517744773","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:07:31Z","timestamp":1777496851000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0022034517744773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,15]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1177\/0022034517744773"],"URL":"https:\/\/doi.org\/10.1177\/0022034517744773","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,15]]}}}