{"data":{"id":"10.25384/sage.c.4118459","type":"dois","attributes":{"doi":"10.25384/sage.c.4118459","prefix":"10.25384","suffix":"sage.c.4118459","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"M. Wolf","affiliation":[],"nameIdentifiers":[]},{"name":"M. Ao","affiliation":[],"nameIdentifiers":[]},{"name":"M.B. Chavez","affiliation":[],"nameIdentifiers":[]},{"name":"T.N. Kolli","affiliation":[],"nameIdentifiers":[]},{"name":"V. Thumbigere-Math","affiliation":[],"nameIdentifiers":[]},{"name":"K. Becker","affiliation":[],"nameIdentifiers":[]},{"name":"E.Y. Chu","affiliation":[],"nameIdentifiers":[]},{"name":"A. Jäger","affiliation":[],"nameIdentifiers":[]},{"name":"M.J. Somerman","affiliation":[],"nameIdentifiers":[]},{"name":"B.L. Foster","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Reduced Orthodontic Tooth Movement in \u003ci\u003eEnpp1\u003c/i\u003e Mutant Mice with Hypercementosis"}],"publisher":"Figshare","container":{},"publicationYear":2018,"subjects":[{"subject":"110599 Dentistry not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"91299 Materials Engineering not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Materials engineering","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"}],"contributors":[],"dates":[{"date":"2018-05-31","dateType":"Created"},{"date":"2018-05-31","dateType":"Updated"},{"date":"2018","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1177/0022034518759295","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"CC BY 4.0","rightsUri":"https://creativecommons.org/licenses/by/4.0"}],"descriptions":[{"description":"Previous studies revealed that cementum formation is tightly regulated by inorganic pyrophosphate (PP\u003csub\u003ei\u003c/sub\u003e), a mineralization inhibitor. Local PP\u003csub\u003ei\u003c/sub\u003e concentrations are determined by regulators, including ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which increases PP\u003csub\u003ei\u003c/sub\u003e concentrations by adenosine triphosphate hydrolysis. Orthodontic forces stimulate alveolar bone remodelling, leading to orthodontic tooth movement (OTM). To better understand how disturbed mineral metabolism and the resulting altered periodontal structures affect OTM, we employed \u003ci\u003eEnpp1\u003c/i\u003e mutant mice that feature reduced PP\u003csub\u003ei\u003c/sub\u003e and increased cervical cementum in a model of OTM induced by a stretched closed-coil spring ligated between the maxillary left first molar and maxillary incisors. We analyzed tooth movement, osteoclast/odontoclast response, and tooth root resorption by micro–computed tomography, histology, histomorphometry, and immunohistochemistry. Preoperatively, we noted an altered periodontium in \u003ci\u003eEnpp1\u003c/i\u003e mutant mice, with significantly increased periodontal ligament (PDL) volume and thickness, as well as increased PDL-bone/tooth root surface area, compared to wild-type (WT) controls. After 11 d of orthodontic treatment, \u003ci\u003eEnpp1\u003c/i\u003e mutant mice displayed 38% reduced tooth movement versus WT mice. Molar roots in \u003ci\u003eEnpp1\u003c/i\u003e mutant mice exhibited less change in PDL width in compression and tension zones compared to WT mice. Root resorption was noted in both groups with no difference in average depths, but resorption lacunae in \u003ci\u003eEnpp1\u003c/i\u003e mutant mice were almost entirely limited to cementum, with 150% increased cementum resorption and 92% decreased dentin resorption. Osteoclast/odontoclast cells were reduced by 64% in \u003ci\u003eEnpp1\u003c/i\u003e mutant mice, with a predominance of tartrate-resistant acid phosphatase (TRAP)–positive cells on root surfaces, compared to WT mice. Increased numbers of TRAP-positive cells on root surfaces were associated with robust immunolocalization of osteopontin (OPN) and receptor-activator of NF-κB ligand (RANKL). Collectively, reduced response to orthodontic forces, decreased tooth movement, and altered osteoclast/odontoclast distribution suggests \u003ci\u003eEnpp1\u003c/i\u003e loss of function has direct effects on clastic function/recruitment and/or indirect effects on periodontal remodeling via altered periodontal structure or tissue mineralization.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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