{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:45:57Z","timestamp":1790052357014,"version":"4.0.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT 180575"],"award-info":[{"award-number":["PJT 180575"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 506294"],"award-info":[{"award-number":["MOP 506294"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Dent. Med"],"abstract":"<jats:p>The attachment of the roots of mammalian teeth of limited eruption to the jawbone is reliant in part on the mineralization of collagen fibrils of the periodontal ligament (PDL) at their entry into bone and cementum as Sharpey's fibers. In periodontitis, a high prevalence infection of periodontal tissues, the attachment apparatus of PDL to the tooth root is progressively destroyed. Despite the pervasiveness of periodontitis and its attendant healthcare costs, and regardless of decades of research into various possible treatments, reliable restoration of periodontal attachment after surgery is not achievable. Notably, treatment outcomes in animal studies have often demonstrated more positive regenerative outcomes than in human clinical studies. Conceivably, defining how species diversity affects cementogenesis and cementum\/PDL regeneration could be instructive for informing novel and more efficacious treatment strategies. Here we briefly review differences in cementum and PDL attachment in commonly used animal models to consider how species differences may lead to enhanced regenerative outcomes.<\/jats:p>","DOI":"10.3389\/fdmed.2023.1124968","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T05:29:06Z","timestamp":1678166946000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Periodontal regeneration: Lessons from the periodontal ligament-cementum junction in diverse animal models"],"prefix":"10.3389","volume":"4","author":[{"given":"Eli D.","family":"Sone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"McCulloch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/j.1600-0757.1997.tb00095.x","article-title":"Dental cementum: the dynamic tissue covering of the root","volume":"13","author":"Bosshardt","year":"1997","journal-title":"Periodontol 2000"},{"key":"B2","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1111\/jcpe.12532","article-title":"Our periodontal tissue: a masterpiece of evolution","volume":"43","author":"Diekwisch","year":"2016","journal-title":"J Clin Periodontol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1111\/j.1600-0757.1997.tb00094.x","article-title":"The periodontal ligament: a unique, multifunctional connective tissue","volume":"13","author":"Beertsen","year":"1997","journal-title":"Periodontol 2000"},{"key":"B4","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1034\/j.1600-0757.2000.2240113.x","article-title":"Tissue engineering: a new paradigm for periodontal regeneration based on molecular and cell biology","volume":"24","author":"Bartold","year":"2000","journal-title":"Periodontol 2000"},{"key":"B5","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1111\/j.1600-0757.2006.00155.x","article-title":"Bone morphogenetic proteins and the induction of periodontal tissue regeneration","volume":"41","author":"Ripamonti","year":"2006","journal-title":"Periodontol 2000"},{"key":"B6","doi-asserted-by":"publisher","first-page":"8574","DOI":"10.1016\/j.biomaterials.2010.06.026","article-title":"Periodontal regeneration using engineered bone marrow mesenchymal stromal cells","volume":"31","author":"Yang","year":"2010","journal-title":"Biomaterials"},{"key":"B7","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1111\/j.1600-0765.2012.01478.x","article-title":"Growth and differentiation factors for periodontal regeneration: a review on factors with clinical testing","volume":"47","author":"Stavropoulos","year":"2012","journal-title":"J Periodontal Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/prd.12091","article-title":"Wound models for periodontal and bone regeneration: the role of biologic research","volume":"68","author":"Sculean","year":"2015","journal-title":"Periodontol 2000"},{"key":"B9","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1111\/prd.12062","article-title":"Cementum proteins: role in cementogenesis, biomineralization, periodontium formation and regeneration","volume":"67","author":"Arzate","year":"2015","journal-title":"Periodontol 2000"},{"key":"B10","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/clr.12543","article-title":"Cell-to-cell communication\u2013periodontal regeneration","volume":"26","author":"Bosshardt","year":"2015","journal-title":"Clin Oral Implants Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fdmed.2021.769134","article-title":"The role of Wnt signaling in postnatal tooth root development","volume":"2","author":"Tokavanich","year":"2021","journal-title":"Front Dent Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1002\/jbmr.1552","article-title":"Genetic evidence for the vital function of Osterix in cementogenesis","volume":"27","author":"Cao","year":"2012","journal-title":"J Bone Miner Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1002\/(SICI)1097-0185(199606)245:2%3C267::AID-AR12%3E3.0.CO;2-N","article-title":"Cementogenesis reviewed: a comparison between human premolars and rodent molars","volume":"245","author":"Bosshardt","year":"1996","journal-title":"Anat Rec"},{"key":"B14","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1111\/j.1600-0765.2008.01158.x","article-title":"Cementogenesis and the induction of periodontal tissue regeneration by the osteogenic proteins of the transforming growth factor-beta superfamily","volume":"44","author":"Ripamonti","year":"2009","journal-title":"J Periodontal Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1111\/jre.12356","article-title":"Redefining the induction of periodontal tissue regeneration in primates by the osteogenic proteins of the transforming growth factor-beta supergene family","volume":"51","author":"Ripamonti","year":"2016","journal-title":"J Periodontal Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1177\/00220345211001848","article-title":"From bite to byte: dental structures resolved at a single-cell resolution","volume":"100","author":"Fresia","year":"2021","journal-title":"J Dent Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.jprot.2013.08.016","article-title":"Proteomic analysis of human dental cementum and alveolar bone","volume":"91","author":"Salmon","year":"2013","journal-title":"J Proteomics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/BF02405332","article-title":"The inhibitory effect of cartilage proteoglycans on hydroxyapatite growth","volume":"36","author":"Chen","year":"1984","journal-title":"Calcif Tissue Int"},{"key":"B19","doi-asserted-by":"publisher","first-page":"4670","DOI":"10.1021\/cr0782729","article-title":"Phosphorylated proteins and control over apatite nucleation, crystal growth, and inhibition","volume":"108","author":"George","year":"2008","journal-title":"Chem Rev"},{"key":"B20","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1111\/j.1600-0765.2005.00800.x","article-title":"Distinctive localization and function for lumican, fibromodulin and decorin to regulate collagen fibril organization in periodontal tissues","volume":"40","author":"Matheson","year":"2005","journal-title":"J Periodont Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1002\/(SICI)1097-0185(199606)245:2%3C293::AID-AR13%3E3.0.CO;2-K","article-title":"Extracellular matrix in tooth cementum and mantle dentin: localization of osteopontin and other noncollagenous proteins, plasma proteins, and glycoconjugates by electron microscopy","volume":"245","author":"McKee","year":"1996","journal-title":"Anat Rec"},{"key":"B22","first-page":"724","article-title":"Biochemical characterisation of proteoglycans from healthy and diseased human cementum","volume":"77","author":"Ababneh","year":"1998","journal-title":"J Dent Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3109\/03008209609021494","article-title":"Differential distribution of lumican and fibromodulin in tooth cementum","volume":"34","author":"Cheng","year":"1996","journal-title":"Conn Tissue Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/(SICI)1097-0185(199801)250:1%3C13::AID-AR3%3E3.0.CO;2-F","article-title":"Developmental appearance and distribution of bone sialoprotein and osteopontin in human and rat cementum","volume":"250","author":"Bosshardt","year":"1998","journal-title":"Anat Rec"},{"key":"B25","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1006\/jsbi.1999.4137","article-title":"Content and distribution of noncollagenous matrix proteins in bone and cementum: relationship to speed of formation and collagen packing density","volume":"126","author":"Nanci","year":"1999","journal-title":"J Struct Biol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s00223-001-1121-z","article-title":"Osteopontin deficiency increases mineral content and mineral crystallinity in mouse bone","volume":"71","author":"Boskey","year":"2002","journal-title":"Calcif Tissue Int"},{"key":"B27","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1007\/s002239900339","article-title":"Effects of bone CS-proteoglycans, DS-decorin, and DS-biglycan on hydroxyapatite formation in a gelatin gel","volume":"61","author":"Boskey","year":"1997","journal-title":"Calcif Tissue Int"},{"key":"B28","doi-asserted-by":"publisher","first-page":"8562","DOI":"10.1073\/pnas.90.18.8562","article-title":"Nucleation of hydroxyapatite by bone sialoprotein","volume":"90","author":"Hunter","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B29","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/0022-0248(94)90501-0","article-title":"Oriented growth of octacalcium phosphate crystals on type-I collagen fibrils under physiological conditions","volume":"140","author":"Iijima","year":"1994","journal-title":"J Cryst Growth"},{"key":"B30","first-page":"489","article-title":"Modified dentine phosphoprotein and proteoglycans influence hydroxyapaptite induced crystal growth","volume":"82","author":"Milan","year":"2003","journal-title":"J Dent Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"4906","DOI":"10.1002\/adfm.201203760","article-title":"Extracellular matrix control of collagen mineralization in vitro","volume":"23","author":"Lausch","year":"2013","journal-title":"Adv Funct Mater"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1021\/acs.biomac.5b00287","article-title":"A top-down approach to elucidate the role of matrix-bound phosphoproteins in control of collagen biomineralization","volume":"16","author":"Lausch","year":"2015","journal-title":"Biomacromolecules"},{"key":"B33","doi-asserted-by":"publisher","first-page":"12636","DOI":"10.1073\/pnas.1914899117","article-title":"Glycosaminoglycans accelerate biomimetic collagen mineralization in a tissue-based in vitro model","volume":"117","author":"Wojtas","year":"2020","journal-title":"Proc Nat Acad Sci USA"},{"key":"B34","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1111\/j.1600-0757.2006.00162.x","article-title":"Regeneration of periodontal tissues: cementogenesis revisited","volume":"41","author":"Zeichner-David","year":"2006","journal-title":"Periodontol 2000"},{"key":"B35","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1111\/jre.12808","article-title":"Comparative proteomic analysis of dental cementum from deciduous and permanent teeth","volume":"56","author":"Giovani","year":"2021","journal-title":"J Periodontal Res"},{"key":"B36","first-page":"267","article-title":"Hexosamine and acid glycosaminoglycans in human teeth","volume":"101","author":"Clark","year":"1965","journal-title":"Biochim Biophys Acta"},{"key":"B37","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3109\/03008209909005276","article-title":"Identification and immunolocalization of chondroitin sulfate proteoglycans in tooth cementum","volume":"40","author":"Cheng","year":"1999","journal-title":"Connect Tissue Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s00441-004-0896-4","article-title":"Immunolocation of proteoglycans and bone-related noncollagenous glycoproteins in developing acellular cementum of rat molars","volume":"317","author":"Yamamoto","year":"2004","journal-title":"Cell Tissue Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1002\/(SICI)1097-0185(19990401)254:4%3C465::AID-AR2%3E3.0.CO;2-8","article-title":"Histochemical studies of glycosaminoglycans in developing periodontal ligaments of ICR mice","volume":"254","author":"Fujii","year":"1999","journal-title":"Anat Rec"},{"key":"B40","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3109\/03008209509016977","article-title":"The effect of glycosylaminoglycans on the mineralization of sheep periodontal ligament in vitro","volume":"33","author":"Kirkham","year":"1995","journal-title":"Connect Tissue Res"},{"key":"B41","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/0003-9969(70)90065-8","article-title":"Isolation and characterization of acid mucopolysaccharides of bovine periodontal membrane","volume":"15","author":"Munemoto","year":"1970","journal-title":"Arch Oral Biol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1034\/j.1600-0765.2001.00607.x","article-title":"Occlusal hypofunction causes changes of proteoglycan content in the rat periodontal ligament","volume":"36","author":"Kaneko","year":"2001","journal-title":"J Periodontal Res"},{"key":"B43","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1034\/j.1600-0765.2002.90770.x","article-title":"Distribution pattern of versican, link protein and hyaluronic acid in the rat periodontal ligament during experimental tooth movement","volume":"37","author":"Sato","year":"2002","journal-title":"J Periodontal Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s00223-004-0033-0","article-title":"Modulation of collagen fibrillogenesis by dentinal proteoglycans","volume":"76","author":"Milan","year":"2005","journal-title":"Calcif Tissue Int"},{"key":"B45","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s00223-004-0273-z","article-title":"Dentinal proteoglycans demonstrate an increasing order of affinity for hydroxyapatite crystals during the transition of predentine to dentine","volume":"75","author":"Milan","year":"2004","journal-title":"Calcif Tissue Int"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e23474","DOI":"10.1002\/dvg.23474","article-title":"Between a rock and a hard place: regulation of mineralization in the periodontium","volume":"60","author":"Andras","year":"2022","journal-title":"Genesis"},{"key":"B47","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1177\/00220345221126716","article-title":"Bone sialoprotein is critical for alveolar bone healing in mice","volume":"102","author":"Chavez","year":"2023","journal-title":"J Dent Res"},{"key":"B48","doi-asserted-by":"publisher","first-page":"115329","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"},{"key":"B49","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1177\/00220345211005677","article-title":"Delivery of alkaline phosphatase promotes periodontal regeneration in mice","volume":"100","author":"Nagasaki","year":"2021","journal-title":"J Dent Res"},{"key":"B50","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1902\/jop.1976.47.5.256","article-title":"On the repair potential of periodontal tissues","volume":"47","author":"Melcher","year":"1976","journal-title":"J Periodontol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1242\/dev.201203","article-title":"Plap-1 lineage tracing and single-cell transcriptomics reveal cellular dynamics in the periodontal ligament","volume":"149","author":"Iwayama","year":"2022","journal-title":"Development"},{"key":"B52","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1111\/jcpe.13666","article-title":"Axin2-expressing cells in the periodontal ligament are regulated by bone morphogenetic protein signalling and play a pivotal role in periodontium development","volume":"49","author":"Xie","year":"2022","journal-title":"J Clin Periodontol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1002\/stem.3288","article-title":"Stem cell contributions to cementoblast differentiation in healthy periodontal ligament and periodontitis","volume":"39","author":"Zhao","year":"2021","journal-title":"Stem Cells"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14445","article-title":"Screening of functionalized collagen membranes with a porcine periodontal regeneration model","author":"Quan","year":"2022","journal-title":"Oral Dis"},{"key":"B55","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1089\/ten.teb.2020.0384","article-title":"Characteristics of large animal models for current cell-based oral tissue regeneration","volume":"28","author":"Mangione","year":"2022","journal-title":"Tissue Eng Part B Rev"}],"container-title":["Frontiers in Dental Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fdmed.2023.1124968\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T15:16:10Z","timestamp":1722266170000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fdmed.2023.1124968\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":55,"alternative-id":["10.3389\/fdmed.2023.1124968"],"URL":"https:\/\/doi.org\/10.3389\/fdmed.2023.1124968","relation":{},"ISSN":["2673-4915"],"issn-type":[{"value":"2673-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,7]]},"article-number":"1124968"}}