ArticlePloS one2012
Central role of pyrophosphate in acellular cementum formation.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 144 citations in OpenAlex.
- Article
- Effects of comorbid chronic kidney disease on late-onset hypophosphatasia mice under treatment with asfotase alfa.JBMR plus · 2026Article
- Loss of PTH 1 receptor signaling in periodontal cells drives cementum dysfunction and molar ankylosis in mice.Bone research · 2026Article
- Hypophosphatasia-pathophysiological understanding, preclinical data looking beyond the skeleton, and upcoming treatments.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Review
- Pyrophosphate Regulates Multilineage Differentiation in Stem Cells From Human Exfoliated Deciduous Teeth.Clinical and experimental dental research · 2025Article
- Reduced orthodontic tooth movement inJBMR plus · 2025Article
- Preclinical evaluation of the efficacy and safety of adeno-associated virus 8-tissue-nonspecific alkaline phosphatase-D10 in Alpl-/- and AlplPrx1/Prx1 mouse models for the treatment of early and late-onset hypophosphatasia.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Review
- A Case of Hypophosphatasia Started Enzyme Replacement Therapy Since Babyhood Stage.Children (Basel, Switzerland) · 2025Article
- Decade-long delayed diagnosis of hypophosphatasia until next generation tooth loss: case reports on dental rehabilitation, diagnostic challenges and clinical implications.Frontiers in oral health · 2025Article
- Establishment of human periodontal ligament cell lines withFrontiers in cell and developmental biology · 2025Article
- Cementum regeneration strategies: Insights from development and periodontal microenvironment.Frontiers in cell and developmental biology · 2025Review
- Deficiency of Trps1 in Cementoblasts Impairs Cementogenesis and Tooth Root Formation.Calcified tissue international · 2024Article
- Inherited phosphate and pyrophosphate disorders: New insights and novel therapies changing the oral health landscape.Journal of the American Dental Association (1939) · 2024Review
- Exosomes: new targets for understanding axon guidance in the developing central nervous system.Frontiers in cell and developmental biology · 2024Review
- Regulation of TGF-β1-induced fibroblast differentiation of human periodontal ligament stem cells through the mutually antagonistic action of ectonucleotide pyrophosphatase/phosphodiesterase 1 and 2.Frontiers in cell and developmental biology · 2024Article
- Hypoalkaline Phosphatemia Dental Type: A Case Report.Clinical medicine insights. Pediatrics · 2024Article
- Periodontal Disease Monitoring by Raman Spectroscopy of Phosphates: New Insights into Pyrophosphate Activity.Diagnostics (Basel, Switzerland) · 2023Article
- Article
- Dentoalveolar Alterations in an Adenine-Induced Chronic Kidney Disease Mouse Model.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundInorganic pyrophosphate (PP(i)) is a physiologic inhibitor of hydroxyapatite mineral precipitation involved in regulating mineralized tissue development and pathologic calcification. Local levels of PP(i) are controlled by antagonistic functions of factors that decrease PP(i) and promote mineralization (tissue-nonspecific alkaline phosphatase, Alpl/TNAP), and those that increase local PP(i) and restrict mineralization (progressive ankylosis protein, ANK; ectonucleotide pyrophosphatase phosphodiesterase-1, NPP1). The cementum enveloping the tooth root is essential for tooth function by providing attachment to the surrounding bone via the nonmineralized periodontal ligament. At present, the developmental regulation of cementum remains poorly understood, hampering efforts for regeneration. To elucidate the role of PP(i) in cementum formation, we analyzed root development in knock-out ((-/-)) mice featuring PP(i) dysregulation.
resultsExcess PP(i) in the Alpl(-/-) mouse inhibited cementum formation, causing root detachment consistent with premature tooth loss in the human condition hypophosphatasia, though cementoblast phenotype was unperturbed. Deficient PP(i) in both Ank and Enpp1(-/-) mice significantly increased cementum apposition and overall thickness more than 12-fold vs. controls, while dentin and cellular cementum were unaltered. Though PP(i) regulators are widely expressed, cementoblasts selectively expressed greater ANK and NPP1 along the root surface, and dramatically increased ANK or NPP1 in models of reduced PP(i) output, in compensatory fashion. In vitro mechanistic studies confirmed that under low PP(i) mineralizing conditions, cementoblasts increased Ank (5-fold) and Enpp1 (20-fold), while increasing PP(i) inhibited mineralization and associated increases in Ank and Enpp1 mRNA.
conclusionsResults from these studies demonstrate a novel developmental regulation of acellular cementum, wherein cementoblasts tune cementogenesis by modulating local levels of PP(i), directing and regulating mineral apposition. These findings underscore developmental differences in acellular versus cellular cementum, and suggest new approaches for cementum regeneration.
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