{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:55:15Z","timestamp":1753876515544,"version":"3.41.2"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["2031\/7-1","1188\/8-1"],"award-info":[{"award-number":["2031\/7-1","1188\/8-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R00DE031148"],"award-info":[{"award-number":["R00DE031148"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"publisher","award":["R01DE027639"],"award-info":[{"award-number":["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","id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023288","name":"German Society of Orthodontics","doi-asserted-by":"publisher","award":["92\/2014"],"award-info":[{"award-number":["92\/2014"]}],"id":[{"id":"10.13039\/501100023288","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Habilitation Program of Faculty of Medicine RWTH Aachen University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypercementosis has been previously reported in mice lacking progressive ankylosis protein (Ank KO mice, or Ank, KO - knockout, WT - wildtype) due to decreased levels of the mineralization inhibitor inorganic pyrophosphate. However, the impact of hypercementosis on alveolar bone remodeling and periodontal ligament (PDL) maintenance from orthodontic forces during orthodontic tooth movement (OTM) remains unclear. To investigate the roles of ANK protein on tooth movement, PDL maintenance, alveolar bone remodeling, and tooth root resorption, we performed a split-mouth model of OTM induced by a closed-coil spring stretched between the maxillary first molar and maxillary incisors in Ank KO and WT mice (including both males and females). Micro-computed tomographic analysis revealed a 36.6% reduction in OTM in Ank KO mice compared with WT mice, although OTM-induced thickening of PDL was found to be similar in both groups. While reduced tissue mineral density (TMD) of the alveolar bone was observed in WT mice, TMD in Ank KO mice was maintained. Loss of Ank leads to wider roots with thicker cementum on the untreated, contralateral side, whereas a significant increase in OTM-induced root resorption was observed on the lateral tension side. Histologic analysis of root resorption confirmed these data and showed increased resorption lacunae located prevalently in the OTM tooth root cementum of Ank KO mice. Using a quantitative PCR array of bone-associated markers to interrogate total RNA harvested from PDL tissues along the root surface, we found alterations in gene expression from OTM in both WT and Ank KO mice, which included genes involved in bone remodeling, calciotropic hormones and receptors, cytokines, growth factors, and receptors. Our findings advance the understanding of the role of Ank in regulating mineralization in the periodontium as well as factors involved in root resorption.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziaf064","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T14:31:12Z","timestamp":1744900272000},"source":"Crossref","is-referenced-by-count":0,"title":["Reduced orthodontic tooth movement in <i>Ank<\/i> knockout mice"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0093-8934","authenticated-orcid":false,"given":"Marta","family":"Rizk","sequence":"first","affiliation":[{"name":"Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily Yin","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Biomaterials and Regenerative Dental Medicine, University of Maryland School of Dentistry , Baltimore, MD 21201-1786 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0768-935X","authenticated-orcid":false,"given":"Rogerio Bastos","family":"Craveiro","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merve","family":"Elmas","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sihem","family":"Brenji","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Niederau","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-634X","authenticated-orcid":false,"given":"Nikolaus","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I\u2014Cardiology, Angiology and Intensive Care Medicine, University Hospital RWTH Aachen , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3444-0576","authenticated-orcid":false,"given":"Brian Lee","family":"Foster","sequence":"additional","affiliation":[{"name":"Division of Biosciences, College of Dentistry, The Ohio State University , Columbus, OH 43210-1267 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha Joan","family":"Somerman","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health , Bethesda, MD 20892-3675 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5882-3080","authenticated-orcid":false,"given":"Michael","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"issue":"6","key":"2025052713275856900_ref1","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/S1079-2104(99)70002-8","article-title":"Dental root resorption","volume":"88","author":"Gunraj","year":"1999","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"issue":"1","key":"2025052713275856900_ref2","doi-asserted-by":"publisher","first-page":"e2001269","DOI":"10.1002\/adhm.202001269","article-title":"Current trends in in vitro modeling to mimic cellular crosstalk in periodontal tissue","volume":"10","author":"Aveic","year":"2021","journal-title":"Adv Healthc Mater"},{"issue":"4","key":"2025052713275856900_ref3","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s00223-012-9672-8","article-title":"The role of phosphatases in the initiation of skeletal mineralization","volume":"93","author":"Mill\u00e1n","year":"2013","journal-title":"Calcif Tissue Int"},{"issue":"6","key":"2025052713275856900_ref4","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1359\/jbmr.2003.18.6.994","article-title":"Linked deficiencies in extracellular PPi and osteopontin mediate pathologic calcification associated with defective PC-1 and ANK expression","volume":"18","author":"Johnson","year":"2003","journal-title":"J Bone Miner Res"},{"issue":"8","key":"2025052713275856900_ref5","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1359\/jbmr.060515","article-title":"Mineral formation in joints caused by complete or joint-specific loss of ANK function","volume":"21","author":"Gurley","year":"2006","journal-title":"J Bone Miner Res"},{"issue":"7","key":"2025052713275856900_ref6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008884","article-title":"The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP","volume":"16","author":"Szeri","year":"2020","journal-title":"PLoS Genet"},{"issue":"5","key":"2025052713275856900_ref7","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1002\/jbmr.4528","article-title":"The mineralization regulator ANKH mediates cellular efflux of ATP","volume":"37","author":"Szeri","year":"2022","journal-title":"J Bone Miner Res"},{"issue":"6","key":"2025052713275856900_ref8","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1359\/jbmr.1999.14.6.883","article-title":"Matrix vesicle plasma cell membrane glycoprotein-1 regulates mineralization by murine osteoblastic MC3T3 cells","volume":"14","author":"Johnson","year":"1999","journal-title":"J Bone Miner Res"},{"issue":"8","key":"2025052713275856900_ref9","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1177\/0022034518759295","article-title":"Reduced orthodontic tooth movement in Enpp1 mutant mice with hypercementosis","volume":"97","author":"Wolf","year":"2018","journal-title":"J Dent Res"},{"issue":"2","key":"2025052713275856900_ref10","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/ar143","article-title":"The Ank gene story","volume":"3","author":"Ryan","year":"2001","journal-title":"Arthritis Res Ther"},{"issue":"4","key":"2025052713275856900_ref11","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/S0002-9440(10)63208-7","article-title":"Concerted regulation of inorganic pyrophosphate and osteopontin by Akp2, Enpp1, and Ank: an integrated model of the pathogenesis of mineralization disorders","volume":"164","author":"Harmey","year":"2004","journal-title":"Am J Pathol"},{"issue":"2","key":"2025052713275856900_ref12","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/j.1601-6343.2007.00387.x","article-title":"Potential role of PC-1 expression and pyrophosphate elaboration in the molecular etiology of the FGFR-associated craniosynostosis syndromes","volume":"10","author":"Hatch","year":"2007","journal-title":"Orthod Craniofacial Res"},{"issue":"6","key":"2025052713275856900_ref13","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.archoralbio.2009.02.011","article-title":"Structure and mechanical properties of Ank\/Ank mutant mouse dental tissues\u2014an animal model for studying periodontal regeneration","volume":"54","author":"Fong","year":"2009","journal-title":"Arch Oral Biol"},{"key":"2025052713275856900_ref14","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.bone.2017.08.027","article-title":"Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis","volume":"105","author":"Ao","year":"2017","journal-title":"Bone"},{"key":"2025052713275856900_ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115329","article-title":"Genetic and pharmacologic modulation of cementogenesis via pyrophosphate regulators","volume":"136","author":"Chu","year":"2020","journal-title":"Bone"},{"issue":"6","key":"2025052713275856900_ref16","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1177\/0022034520981854","article-title":"Ablation of pyrophosphate regulators promotes periodontal regeneration","volume":"100","author":"Nagasaki","year":"2021","journal-title":"J Dent Res"},{"issue":"6","key":"2025052713275856900_ref17","doi-asserted-by":"publisher","first-page":"e38393","DOI":"10.1371\/journal.pone.0038393","article-title":"Central role of pyrophosphate in acellular cementum formation","volume":"7","author":"Foster","year":"2012","journal-title":"PLoS One"},{"issue":"6","key":"2025052713275856900_ref18","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1177\/0022034514529304","article-title":"Dental anomalies associated with craniometaphyseal dysplasia","volume":"93","author":"Chen","year":"2014","journal-title":"J Dent Res"},{"issue":"4","key":"2025052713275856900_ref19","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1177\/0022034517744773","article-title":"Hypercementosis associated with ENPP1 mutations and GACI","volume":"97","author":"Thumbigere-Math","year":"2018","journal-title":"J Dent Res"},{"key":"2025052713275856900_ref20","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.archoralbio.2018.08.003","article-title":"Expression of biological mediators during orthodontic tooth movement: a systematic review","volume":"95","author":"Vansant","year":"2018","journal-title":"Arch Oral Biol"},{"issue":"5","key":"2025052713275856900_ref21","doi-asserted-by":"publisher","first-page":"3911","DOI":"10.1007\/s00784-021-04358-w","article-title":"3D Quantification of in vivo orthodontic tooth movement in rats by means of micro-computed tomography","volume":"26","author":"Cadenas de Llano-P\u00e9rula","year":"2022","journal-title":"Clin Oral Investig"},{"issue":"1","key":"2025052713275856900_ref22","doi-asserted-by":"publisher","first-page":"19919","DOI":"10.1038\/s41598-023-47386-0","article-title":"Periodontal ligament and alveolar bone remodeling during long orthodontic tooth movement analyzed by a novel user-independent 3D-methodology","volume":"13","author":"Rizk","year":"2023","journal-title":"Sci Rep"},{"issue":"6","key":"2025052713275856900_ref23","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1046\/j.0909-8836.1999.eos107608.x","article-title":"Tooth movement with light continuous and discontinuous forces in beagle dogs","volume":"107","author":"Van Leeuwen","year":"1999","journal-title":"Eur J Oral Sci"},{"issue":"5","key":"2025052713275856900_ref24","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.ejwf.2022.08.003","article-title":"Neural regulation of alveolar bone remodeling and periodontal ligament metabolism during orthodontic tooth movement in response to therapeutic loading","volume":"11","author":"Zhang","year":"2022","journal-title":"J World Fed Orthodontists"},{"issue":"5","key":"2025052713275856900_ref25","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.3390\/nu12051471","article-title":"Vitamin D deficiency and oral health: a comprehensive review","volume":"12","author":"Botelho","year":"2020","journal-title":"Nutrients"},{"issue":"1","key":"2025052713275856900_ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2020.107597","article-title":"Insights into dental mineralization from three heritable mineralization disorders","volume":"212","author":"Chavez","year":"2020","journal-title":"J Struct Biol"},{"issue":"5","key":"2025052713275856900_ref27","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.3390\/ijms22052388","article-title":"Is inflammation a friend or foe for orthodontic treatment?: inflammation in orthodontically induced inflammatory root resorption and accelerating tooth movement","volume":"22","author":"Yamaguchi","year":"2021","journal-title":"IJMS"},{"issue":"1","key":"2025052713275856900_ref28","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s00784-009-0263-7","article-title":"Anabolic effect of intermittent PTH(1-34) on the local microenvironment during the late phase of periodontal repair in a rat model of tooth root resorption","volume":"14","author":"Lossd\u00f6rfer","year":"2010","journal-title":"Clin Oral Invest"},{"issue":"3","key":"2025052713275856900_ref29","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1111\/jre.12309","article-title":"Gene-expression analysis of cementoblasts and osteoblasts","volume":"51","author":"Matthews","year":"2016","journal-title":"J Periodontal Res"},{"issue":"1","key":"2025052713275856900_ref30","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.metabol.2014.10.021","article-title":"The role of leptin in regulating bone metabolism","volume":"64","author":"Upadhyay","year":"2015","journal-title":"Metabolism"},{"key":"2025052713275856900_ref31","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.steroids.2015.11.011","article-title":"The association between sex hormone-binding globulin gene polymorphism with bone mineral density","volume":"106","author":"Zha","year":"2016","journal-title":"Steroids"},{"key":"2025052713275856900_ref32","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.833485","article-title":"The role of NPY in the regulation of bone metabolism","volume":"13","author":"Chen","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"2025052713275856900_ref33","doi-asserted-by":"publisher","first-page":"5010","DOI":"10.1038\/s41598-023-32221-3","article-title":"Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta","volume":"13","author":"Marulanda","year":"2023","journal-title":"Sci Rep"},{"issue":"10","key":"2025052713275856900_ref34","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1016\/j.joen.2016.07.008","article-title":"Osteoprotegerin-knockout mice developed early onset root resorption","volume":"42","author":"Liu","year":"2016","journal-title":"J Endod"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jbmrplus\/advance-article-pdf\/doi\/10.1093\/jbmrpl\/ziaf064\/62948951\/ziaf064.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/9\/6\/ziaf064\/62948951\/ziaf064.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/9\/6\/ziaf064\/62948951\/ziaf064.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T17:28:02Z","timestamp":1748366882000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/doi\/10.1093\/jbmrpl\/ziaf064\/8115469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,4,30]]}},"URL":"https:\/\/doi.org\/10.1093\/jbmrpl\/ziaf064","relation":{},"ISSN":["2473-4039"],"issn-type":[{"type":"electronic","value":"2473-4039"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,4,17]]},"article-number":"ziaf064"}}