{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:21:53Z","timestamp":1788931313456,"version":"build-2803163510"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T00:00:00Z","timestamp":1442880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\u2010K011421"],"award-info":[{"award-number":["MR\u2010K011421"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003194","name":"New York Stem Cell Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003194","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Cells with in vitro properties similar to those of bone marrow stromal stem cells are present in tooth pulp as quiescent cells that are mobilized by damage. These dental pulp stem cells (DPSCs) respond to damage by stimulating proliferation and differentiation into odontoblast-like cells that form dentine to repair the damage. In continuously growing mouse incisors, tissue at the incisor tips is continuously being damaged by the shearing action between the upper and lower teeth acting to self-sharpen the tips. We investigated mouse incisor tips as a model for the role of DPSCs in a continuous natural repair\/regeneration process. We show that the pulp at the incisor tip is composed of a disorganized mass of mineralized tissue produced by odontoblast-like cells. These cells become embedded into the mineralized tissue that is rapidly formed and then lost during feeding. Tetracycline labeling not only revealed the expected incorporation into newly synthesized dentine formation of the incisor but also a zone covering the pulp cavity at the tips of the incisors that is mineralized very rapidly. This tissue was dentine-like but had a significantly lower mineral content than dentine as determined by Raman spectroscopy. The mineral was more crystalline than dentine, indicative of small, defect-free mineral particles. To identify the origin of cells responsible for deposition of this mineralized tissue, we genetically labeled perivascular cells by crossing NG2ERT2Cre and Nestin Cre mice with reporter mice. A large number of pericyte-derived cells were visible in the pulp of incisor tips with some having elongated, odontoblast-like shapes. These results show that in mouse incisors, rapid, continuous mineralization occurs at the tip to seal off the pulp tissue from the external environment. The mineral is formed by perivascular-derived cells that differentiate into cells expressing dentin sialo-phosphoprotein (DSPP) and produce a dentine-like material in a process that functions as continuous natural tissue regeneration. \u00a9 2015 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2717","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T12:20:51Z","timestamp":1442924451000},"page":"514-523","source":"Crossref","is-referenced-by-count":38,"title":["Perivascular Stem Cells at the Tip of Mouse Incisors Regulate Tissue Regeneration"],"prefix":"10.1093","volume":"31","author":[{"given":"Yvonne WY","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Craniofacial Development and Stem Cell BiologyDental Institute, Guy's Hospital, King's College LondonLondonUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifan","family":"Feng","sequence":"additional","affiliation":[{"name":"Center for Craniofacial Molecular Biology, Ostrow School of DentistryUniversity of Southern CaliforniaLos AngelesCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Daltoe","sequence":"additional","affiliation":[{"name":"Departamento de Patologia, Centro de Ci\u00eancias da Sa\u00fadeUniversidade Federal de Santa Catarina, Campus Universit\u00e1rioTrindadeFlorian\u00f3polisBrasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Fatscher","sequence":"additional","affiliation":[{"name":"Materials Science and Engineering DepartmentState University of New York at Stony BrookStony BrookNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Gentleman","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Development and Stem Cell BiologyDental Institute, Guy's Hospital, King's College LondonLondonUK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly M","family":"Gentleman","sequence":"additional","affiliation":[{"name":"Materials Science and Engineering DepartmentState University of New York at Stony BrookStony BrookNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T","family":"Sharpe","sequence":"additional","affiliation":[{"name":"Department of Craniofacial Development and Stem Cell BiologyDental Institute, Guy's Hospital, King's College LondonLondonUK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,22]]},"reference":[{"issue":"2","key":"2024021014174011500_jbmr2717-bib-0001","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1089\/ten.tea.2009.0518","article-title":"Stem\/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model","volume":"16","author":"Huang","year":"2010","journal-title":"Tissue Eng Part A"},{"issue":"8","key":"2024021014174011500_jbmr2717-bib-0002","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.biocel.2004.01.006","article-title":"Odontoblasts: the cells forming and maintaining dentine","volume":"36","author":"Arana-Chavez","year":"2004","journal-title":"Int J Biochem Cell Biol"},{"issue":"4","key":"2024021014174011500_jbmr2717-bib-0003","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1067\/moe.2002.120974","article-title":"Age-related odontometric changes of human teeth","volume":"93","author":"Murray","year":"2002","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"issue":"2","key":"2024021014174011500_jbmr2717-bib-0004","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.archoralbio.2004.11.009","article-title":"Activation of human dental pulp progenitor\/stem cells in response to odontoblast injury","volume":"50","author":"Tecles","year":"2005","journal-title":"Arch Oral Biol"},{"issue":"1","key":"2024021014174011500_jbmr2717-bib-0005","first-page":"273","article-title":"Reactionary dentinogenesis","volume":"39","author":"Smith","year":"1995","journal-title":"Int J Dev Biol"},{"issue":"2","key":"2024021014174011500_jbmr2717-bib-0006","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1601-0825.2006.01346.x","article-title":"Stem cells and the dental pulp: potential roles in dentine regeneration and repair","volume":"13","author":"Sloan","year":"2007","journal-title":"Oral Dis"},{"issue":"8","key":"2024021014174011500_jbmr2717-bib-0007","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1387\/ijdb.072393hl","article-title":"Coexpression of Notch3 and Rgs5 in the pericyte-vascular smooth muscle cell axis in response to pulp injury","volume":"51","author":"Lovschall","year":"2007","journal-title":"Int J Dev Biol"},{"issue":"2","key":"2024021014174011500_jbmr2717-bib-0008","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/dvg.22732","article-title":"On the cutting edge of organ renewal: identification, regulation, and evolution of incisor stem cells","volume":"52","author":"Kuang-Hsien Hu","year":"2014","journal-title":"Genesis"},{"issue":"1","key":"2024021014174011500_jbmr2717-bib-0009","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1083\/jcb.147.1.105","article-title":"Localization of putative stem cells in dental epithelium and their association with notch and FGF signaling","volume":"147","author":"Harada","year":"1999","journal-title":"J Cell Biol"},{"issue":"22","key":"2024021014174011500_jbmr2717-bib-0010","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1242\/dev.056358","article-title":"Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor","volume":"137","author":"Seidel","year":"2004","journal-title":"Development"},{"issue":"2","key":"2024021014174011500_jbmr2717-bib-0011","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ydbio.2012.04.029","article-title":"Ring1a\/b polycomb proteins regulate the mesenchymal stem cell niche in continuously growing incisors","volume":"367","author":"Lapthanasupkul","year":"2012","journal-title":"Dev Biol"},{"issue":"2","key":"2024021014174011500_jbmr2717-bib-0012","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.stem.2013.12.013","article-title":"Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor","volume":"14","author":"Zhao","year":"2014","journal-title":"Cell Stem Cell"},{"issue":"7519","key":"2024021014174011500_jbmr2717-bib-0013","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nature13536","article-title":"Glial origin of mesenchymal stem cells in a tooth model system","volume":"513","author":"Kaukua","year":"2014","journal-title":"Nature"},{"issue":"5","key":"2024021014174011500_jbmr2717-bib-0014","doi-asserted-by":"crossref","first-page":"697","DOI":"10.2217\/rme.09.45","article-title":"Pulp and dentin tissue engineering and regeneration: current progress","volume":"4","author":"Huang","year":"2009","journal-title":"Regen Med"},{"issue":"Pt 2","key":"2024021014174011500_jbmr2717-bib-0015","first-page":"427","article-title":"On the incremental lines in human dentine as revealed by tetracycline labeling","volume":"123","author":"Kawasaki","year":"1977","journal-title":"J Anat"},{"issue":"8","key":"2024021014174011500_jbmr2717-bib-0016","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1177\/0022034510368647","article-title":"SHED differentiate into functional odontoblasts and endothelium","volume":"89","author":"Sakai","year":"2010","journal-title":"J Dent Res"},{"issue":"Pt 3","key":"2024021014174011500_jbmr2717-bib-0017","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1042\/BST0350544","article-title":"Raman microspectroscopy for non-invasive biochemical analysis of single cells","volume":"35","author":"Swain","year":"2007","journal-title":"Biochem Soc Trans"},{"issue":"1","key":"2024021014174011500_jbmr2717-bib-0018","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/jmor.1050260103","article-title":"The structure and growth of the incisor teeth of the albino rat","volume":"26","author":"Addison","year":"1915","journal-title":"J Morphol"},{"issue":"33","key":"2024021014174011500_jbmr2717-bib-0019","doi-asserted-by":"crossref","first-page":"29717","DOI":"10.1074\/jbc.M502929200","article-title":"Differential regulation of dentin sialophosphoprotein expression by Runx2 during odontoblast cytodifferentiation","volume":"280","author":"Chen","year":"2005","journal-title":"J Biol Chem"},{"issue":"Suppl 1","key":"2024021014174011500_jbmr2717-bib-0020","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/j.1600-0722.1998.tb02184.x","article-title":"Comparative analysis of mouse DSP and DPP expression in odontoblasts, preameloblasts, and experimentally induced odontoblast-like cells","volume":"106","author":"Begue-Kirn","year":"1998","journal-title":"Eur J Oral Sci"},{"issue":"5 Pt 1","key":"2024021014174011500_jbmr2717-bib-0021","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1600-0722.1997.tb02137.x","article-title":"Dentin sialoprotein (DSP) transcripts: developmentally-sustained expression in odontoblasts and transient expression in pre-ameloblasts","volume":"105","author":"Ritchie","year":"1997","journal-title":"Eur J Oral Sci"},{"issue":"16","key":"2024021014174011500_jbmr2717-bib-0022","doi-asserted-by":"crossref","first-page":"6503","DOI":"10.1073\/pnas.1015449108","article-title":"Dual origin of mesenchymal stem cells contributing to organ growth and repair","volume":"108","author":"Feng","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3\u20134","key":"2024021014174011500_jbmr2717-bib-0023","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/1526-968X(200011\/12)28:3\/4<147::AID-GENE90>3.0.CO;2-G","article-title":"Z\/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision","volume":"28","author":"Novak","year":"2000","journal-title":"Genesis"},{"issue":"3","key":"2024021014174011500_jbmr2717-bib-0024","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1136\/jcp.2004.025403","article-title":"Nestin expression in odontoblasts and odontogenic ectomesenchymal tissue of odontogenic tumours","volume":"59","author":"Fujita","year":"2006","journal-title":"J Clin Pathol"},{"issue":"1","key":"2024021014174011500_jbmr2717-bib-0025","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0002-9440(10)64539-7","article-title":"Nestin expression in embryonic and adult human teeth under normal and pathological conditions","volume":"157","author":"About","year":"2000","journal-title":"Am J Pathol"},{"issue":"5","key":"2024021014174011500_jbmr2717-bib-0026","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/sj.jcbfm.9600272","article-title":"CNS microvascular pericytes exhibit multipotential stem cell activity","volume":"26","author":"Dore-Duffy","year":"2006","journal-title":"J Cereb Blood Flow Metab"},{"issue":"10","key":"2024021014174011500_jbmr2717-bib-0027","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1097\/00004770-200310000-00008","article-title":"Identification of hard tissue after experimental pulp capping using dentin sialoprotein (DSP) as a marker","volume":"29","author":"Andelin","year":"2003","journal-title":"J Endod"},{"issue":"1","key":"2024021014174011500_jbmr2717-bib-0028","first-page":"4","article-title":"Tunnel defects in dentin bridges: their formation following direct pulp capping","volume":"21","author":"Cox","year":"1996","journal-title":"Oper Dent"},{"issue":"3","key":"2024021014174011500_jbmr2717-bib-0029","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1601-6343.2005.00331.x","article-title":"The efficacy of mesenchymal stem cells to regenerate and repair dental structures","volume":"8","author":"Shi","year":"2005","journal-title":"Orthod Craniofac Res"},{"issue":"2","key":"2024021014174011500_jbmr2717-bib-0030","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s007840050126","article-title":"Bone sialoprotein-induced reparative dentinogenesis in the pulp of rat's molar","volume":"4","author":"Decup","year":"2000","journal-title":"Clin Oral Investig"},{"issue":"7","key":"2024021014174011500_jbmr2717-bib-0031","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/0003-9969(90)90078-O","article-title":"The induction of reparative dentine in the amputated dental pulp of the dog by bone morphogenetic protein","volume":"35","author":"Nakashima","year":"1990","journal-title":"Arch Oral Biol"},{"issue":"2","key":"2024021014174011500_jbmr2717-bib-0032","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/aja.1001690208","article-title":"A light and electron microscopic study of osteodentin formation in the rat incisor after adriamycin administration","volume":"169","author":"Karim","year":"1984","journal-title":"Am J Anat"},{"issue":"6","key":"2024021014174011500_jbmr2717-bib-0033","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1161\/01.RES.0000182903.16652.d7","article-title":"Endothelial\/pericyte interactions","volume":"97","author":"Armulik","year":"2005","journal-title":"Circ Res"},{"key":"2024021014174011500_jbmr2717-bib-0034","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1038\/emm.2013.94","article-title":"Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine","volume":"45","author":"Murphy","year":"2013","journal-title":"Exp Mol Med"},{"issue":"6","key":"2024021014174011500_jbmr2717-bib-0035","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1002\/stem.1681","article-title":"Concise review: the surface markers and identity of human mesenchymal stem cells","volume":"32","author":"Lv","year":"2014","journal-title":"Stem Cells"},{"issue":"3","key":"2024021014174011500_jbmr2717-bib-0036","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.stem.2008.07.003","article-title":"A perivascular origin for mesenchymal stem cells in multiple human organs","volume":"3","author":"Crisan","year":"2008","journal-title":"Cell Stem Cell"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.2717","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.2717","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/31\/3\/514\/56648445\/jbmr2717.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/31\/3\/514\/56648445\/jbmr2717.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:55:18Z","timestamp":1710341718000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/31\/3\/514-523\/7605022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,22]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,9,22]]},"published-print":{"date-parts":[[2016,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.2717","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2016,3,1]]},"published":{"date-parts":[[2015,9,22]]}}}