{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T15:51:47Z","timestamp":1740153107720,"version":"3.37.3"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T00:00:00Z","timestamp":1547596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/rsc.li\/journals-terms-of-use"}],"funder":[{"DOI":"10.13039\/501100009509","name":"Kementerian Riset Teknologi Dan Pendidikan Tinggi Republik Indonesia","doi-asserted-by":"publisher","award":["Unassigned"],"award-info":[{"award-number":["Unassigned"]}],"id":[{"id":"10.13039\/501100009509","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009509","name":"Kementerian Riset Teknologi Dan Pendidikan Tinggi Republik Indonesia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009509","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Zinc (Zn) is distributed throughout the body and within cells by saturable processes mediated by the transport proteins of the ZnT (SLC30) and ZIP (SLC39) families. The two families function in opposite directions. ZnT transporters mediate cellular zinc efflux or intracellular sequestration. Zn is found in human tooth enamel and dentine at levels that have been related to environmental exposures, such as pollution, disease, and dietary intake. The mechanism by which Zn in the odontoblast is deposited in the hard tissue of the tooth, however, is unknown but is important in determining the physical properties, and hence resilience, of enamel and in the context of the use of tooth zinc level as a biomarker of exposure. We hypothesised that zinc efflux mediated by members of the ZnT family of 10 transporters is a key step in this process and is regulated by zinc availability through effects on mRNA levels. Thus, we determined the profile of ZnT transporter mRNA in a human active-secretory odontoblast-like cell model under conditions of high- and low-extracellular Zn concentration and determined if the same transporter mRNAs were present in human dental pulp. ZnT1, ZnT5 and ZnT9 mRNAs were detected by RT-PCR in both the secretory odontoblast cells and human dental pulp. ZnT2, ZnT3 and ZnT10 mRNAs were not detected, and ZnT4 mRNA was detected in secretory odontoblasts only, which may be indicative of a specialised zinc efflux function during the active secretory phase of tooth development. ZnT1 mRNA was significantly increased in response to extracellular Zn exposure (60 \u03bcM) after 24 h. The presence of Zn transporter mRNAs in secretory odontoblasts and dental pulp indicates that the corresponding transport proteins function to deposit zinc in the dental hard tissues. The responsiveness of ZnT1 in odontoblasts to zinc availability is concordant with this being a process that is regulated to maintain cellular Zn homeostasis and that is a mediator of the relationship between environmental Zn exposure and dental Zn deposition. These findings have likely relevance to human dental health through effects of Zn transporter expression level on the hard tissue properties.<\/jats:p>","DOI":"10.1039\/c8mt00343b","type":"journal-article","created":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T17:34:37Z","timestamp":1547660077000},"page":"613-620","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The presence and response to Zn of ZnT family mRNAs in human dental pulp"],"prefix":"10.1093","volume":"11","author":[{"given":"Nieka A","family":"Wahono","sequence":"first","affiliation":[{"name":"Centre for Oral Health Research and Human Nutrition Research Centre, School of Dental Science, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4BW, UK"},{"name":"Pediatric Dentistry Department, Faculty of Dentistry, Universitas Indonesia, Salemba Raya 4, DKI Jakarta, 10430, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8121-9319","authenticated-orcid":false,"given":"Dianne","family":"Ford","sequence":"additional","affiliation":[{"name":"Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa A","family":"Wakeling","sequence":"additional","affiliation":[{"name":"Centre for Oral Health Research and Human Nutrition Research Centre, School of Dental Science, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4BW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3627-9117","authenticated-orcid":false,"given":"Ruth A","family":"Valentine","sequence":"additional","affiliation":[{"name":"Centre for Oral Health Research and Human Nutrition Research Centre, School of Dental Science, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4BW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,1,16]]},"reference":[{"issue":"3","key":"2021121516070383900_cit1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1152\/physrev.00035.2014","article-title":"The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism","volume":"95","author":"Kambe","year":"2015","journal-title":"Physiol. Rev."},{"issue":"2","key":"2021121516070383900_cit2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s12576-017-0521-4","article-title":"Physiological roles of zinc transporters: molecular and genetic importance in zinc homeostasis","volume":"67","author":"Hara","year":"2017","journal-title":"J. Physiol. Sci."},{"key":"2021121516070383900_cit3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.abb.2016.06.020","article-title":"Zinc transporters and signaling in physiology and pathogenesis","volume":"611","author":"Hojyo","year":"2016","journal-title":"Arch. Biochem. Biophys."},{"issue":"2\u20133","key":"2021121516070383900_cit4","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.mam.2012.05.008","article-title":"The SLC30 family of zinc transporters \u2013 A review of current understanding of their biological and pathophysiological roles","volume":"34","author":"Huang","year":"2013","journal-title":"Mol. Aspects Med."},{"issue":"2\u20133","key":"2021121516070383900_cit5","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.mam.2012.05.011","article-title":"The SLC39 family of zinc transporters","volume":"34","author":"Jeong","year":"2013","journal-title":"Mol. Aspects Med."},{"issue":"8","key":"2021121516070383900_cit6","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1039\/c2mt20088k","article-title":"Efflux function, tissue-specific expression and intracellular trafficking of the Zn transporter ZnT10 indicate roles in adult Zn homeostasis","volume":"4","author":"Bosomworth","year":"2012","journal-title":"Metallomics"},{"issue":"43","key":"2021121516070383900_cit7","doi-asserted-by":"crossref","first-page":"36567","DOI":"10.1074\/jbc.M112.397000","article-title":"Identification of the human zinc transcriptional regulatory element (ZTRE): a palindromic protein-binding DNA sequence responsible for zinc-induced transcriptional repression","volume":"287","author":"Coneyworth","year":"2012","journal-title":"J. Biol. Chem."},{"issue":"19","key":"2021121516070383900_cit8","doi-asserted-by":"crossref","first-page":"14389","DOI":"10.1074\/jbc.M701752200","article-title":"ZnT5 variant B is a bidirectional zinc transporter and mediates zinc uptake in human intestinal Caco-2 cells","volume":"282","author":"Valentine","year":"2007","journal-title":"J. Biol. Chem."},{"issue":"34","key":"2021121516070383900_cit9","doi-asserted-by":"crossref","first-page":"24085","DOI":"10.1074\/jbc.R600011200","article-title":"Mammalian Zinc Transport, Trafficking, and Signals","volume":"281","author":"Cousins","year":"2006","journal-title":"J. Biol. Chem."},{"issue":"4","key":"2021121516070383900_cit10","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1136\/gut.2004.041962","article-title":"Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation","volume":"54","author":"Cragg","year":"2005","journal-title":"Gut"},{"issue":"5\u20136","key":"2021121516070383900_cit11","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.placenta.2006.07.002","article-title":"Zinc Transporters in the Mouse Placenta Show a Coordinated Regulatory Response to Changes in Dietary Zinc Intake","volume":"28","author":"Helston","year":"2007","journal-title":"Placenta"},{"issue":"9","key":"2021121516070383900_cit12","doi-asserted-by":"crossref","first-page":"4841","DOI":"10.1073\/pnas.95.9.4841","article-title":"Regulation of the zinc transporter ZnT-1 by dietary zinc","volume":"95","author":"McMahon","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"12","key":"2021121516070383900_cit13","doi-asserted-by":"crossref","first-page":"6952","DOI":"10.1073\/pnas.0732111100","article-title":"A global view of the selectivity of zinc deprivation and excess on genes expressed in human THP-1 mononuclear cells","volume":"100","author":"Cousins","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021121516070383900_cit14","first-page":"79","volume-title":"Ten Cates Oral Histology; Development, Structure and Function","author":"Nanci","year":"2008","edition":"7th"},{"issue":"3","key":"2021121516070383900_cit15","first-page":"1057","article-title":"Histopathological consequences of hyperzincemia on rat teeth. Experimental study","volume":"57","author":"Scutariu","year":"2016","journal-title":"Rom. J. Morphol. Embryol."},{"key":"2021121516070383900_cit16","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.2147\/IJN.S155228","article-title":"The evaluation of zinc and copper content in tooth enamel without any pathological changes \u2013 an in vitro study","volume":"13","author":"Klimuszko","year":"2018","journal-title":"Int. J. Nanomed."},{"issue":"11","key":"2021121516070383900_cit17","doi-asserted-by":"crossref","first-page":"e3642","DOI":"10.1371\/journal.pone.0003642","article-title":"The zinc transporter SLC39A13\/ZIP13 is required for connective tissue development; its involvement in BMP\/TGF-beta signaling pathways","volume":"3","author":"Fukada","year":"2008","journal-title":"PLoS One"},{"issue":"1","key":"2021121516070383900_cit18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1349-0079(11)80030-7","article-title":"Slc39a13\/Zip13: A Crucial Zinc Transporter Involved in Tooth Development and Inherited Disorders","volume":"53","author":"Fukada","year":"2011","journal-title":"J. Oral Biosci."},{"issue":"8","key":"2021121516070383900_cit19","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.archoralbio.2007.02.006","article-title":"Immortalization and characterization of human dental pulp cells with odontoblastic differentiation","volume":"52","author":"Kitagawa","year":"2007","journal-title":"Arch. Oral Biol."},{"issue":"9","key":"2021121516070383900_cit20","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"issue":"1","key":"2021121516070383900_cit21","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s12011-016-0763-7","article-title":"Promotive Effect of Zinc Ions on the Vitality, Migration, and Osteogenic Differentiation of Human Dental Pulp Cells","volume":"175","author":"An","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"issue":"2","key":"2021121516070383900_cit22","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00774-012-0409-6","article-title":"Zinc signal: a new player in osteobiology","volume":"31","author":"Fukada","year":"2013","journal-title":"J. Bone Miner. Metab."},{"issue":"44","key":"2021121516070383900_cit23","doi-asserted-by":"crossref","first-page":"34803","DOI":"10.1074\/jbc.M007339200","article-title":"The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene","volume":"275","author":"Langmade","year":"2000","journal-title":"J. Biol. Chem."},{"issue":"4","key":"2021121516070383900_cit24","doi-asserted-by":"crossref","first-page":"735","DOI":"10.3945\/an.116.012518","article-title":"Metallothionein and Zinc Transporter Expression in Circulating Human Blood Cells as Biomarkers of Zinc Status: a Systematic Review","volume":"7","author":"Hennigar","year":"2016","journal-title":"Adv. Nutr."},{"issue":"2","key":"2021121516070383900_cit25","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/gene.20067","article-title":"Mouse zinc transporter 1 gene provides an essential function during early embryonic development","volume":"40","author":"Andrews","year":"2004","journal-title":"Genesis"},{"issue":"15","key":"2021121516070383900_cit26","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1093\/hmg\/11.15.1775","article-title":"Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5","volume":"11","author":"Inoue","year":"2002","journal-title":"Hum. Mol. Genet."},{"issue":"11","key":"2021121516070383900_cit27","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1016\/j.bbadis.2017.07.014","article-title":"Loss of synaptic zinc transport in progranulin deficient mice may contribute to progranulin-associated psychopathology and chronic pain","volume":"1863","author":"Hardt","year":"2017","journal-title":"Biochim. Biophys. Acta, Mol. Basis Dis."},{"issue":"25","key":"2021121516070383900_cit28","doi-asserted-by":"crossref","first-page":"22789","DOI":"10.1074\/jbc.M200577200","article-title":"A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane","volume":"277","author":"Cragg","year":"2002","journal-title":"J. Biol. Chem."},{"issue":"45","key":"2021121516070383900_cit29","doi-asserted-by":"crossref","first-page":"30798","DOI":"10.1074\/jbc.M109.026435","article-title":"Demonstration and characterization of the heterodimerization of ZnT5 and ZnT6 in the early secretory pathway","volume":"284","author":"Fukunaka","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021121516070383900_cit30","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jtemb.2018.04.034","article-title":"Expression of zinc transporters ZIP4, ZIP14 and ZnT9 in hepatic carcinogenesis-An immunohistochemical study","volume":"49","author":"Gartmann","year":"2018","journal-title":"J. Trace Elem. Med. Biol."},{"issue":"10","key":"2021121516070383900_cit31","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.archoralbio.2007.04.003","article-title":"The application of synchrotron radiation induced X-ray emission in the measurement of zinc and lead in Wistar rat ameloblasts","volume":"52","author":"Arora","year":"2007","journal-title":"Arch. Oral Biol."},{"volume-title":"Zinc deficiency and its inherited","author":"Ackland","key":"2021121516070383900_cit32"}],"container-title":["Metallomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/metallomics\/article-pdf\/11\/3\/613\/41773474\/c8mt00343b.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/metallomics\/article-pdf\/11\/3\/613\/41773474\/c8mt00343b.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T16:17:38Z","timestamp":1639585058000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/metallomics\/article\/11\/3\/613\/5954244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,16]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3,20]]}},"URL":"https:\/\/doi.org\/10.1039\/c8mt00343b","relation":{},"ISSN":["1756-5901","1756-591X"],"issn-type":[{"type":"print","value":"1756-5901"},{"type":"electronic","value":"1756-591X"}],"subject":[],"published-other":{"date-parts":[[2019,3]]},"published":{"date-parts":[[2019,1,16]]},"assertion":[{"value":"This document is Similarity Check deposited","name":"similarity_check","explanation":{"URL":"https:\/\/www.crossref.org\/services\/similarity-check\/"},"group":{"name":"similarity_check","label":"SIMILARITY CHECK"}},{"value":"Dianne Ford (ORCID)","URL":"http:\/\/orcid.org\/0000-0001-8121-9319","name":"identifier","group":{"name":"author_identifiers","label":"IDENTIFIERS"}},{"value":"Ruth A. Valentine (ORCID)","URL":"http:\/\/orcid.org\/0000-0002-3627-9117","name":"identifier","group":{"name":"author_identifiers","label":"IDENTIFIERS"}},{"value":"Single-blind","order":2,"name":"peer_review_method","group":{"name":"peer_review_method","label":"PEER REVIEW METHOD"}},{"value":"Received 28 November 2018; Accepted 15 January 2019;  Accepted Manuscript published 16 January 2019;  Advance Article published 24 January 2019;  Version of Record published 20 March 2019","order":1,"name":"history","group":{"name":"publication_history","label":"PUBLICATION HISTORY"}}]}}