Central role of pyrophosphate in acellular cementum formation.

<h4>Background</h4>Inorganic 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 decreas...

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Autores principales:	Brian L Foster, Kanako J Nagatomo, Francisco H Nociti, Hanson Fong, Daisy Dunn, Anne B Tran, Wei Wang, Sonoko Narisawa, Jose Luis Millán, Martha J Somerman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12d0fba9e7b44068af999f54a6b83b2c
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spelling	oai:doaj.org-article:12d0fba9e7b44068af999f54a6b83b2c2021-11-18T07:16:25ZCentral role of pyrophosphate in acellular cementum formation.1932-620310.1371/journal.pone.0038393https://doaj.org/article/12d0fba9e7b44068af999f54a6b83b2c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22675556/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Inorganic 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.<h4>Results</h4>Excess 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.<h4>Conclusions</h4>Results 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.Brian L FosterKanako J NagatomoFrancisco H NocitiHanson FongDaisy DunnAnne B TranWei WangSonoko NarisawaJose Luis MillánMartha J SomermanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e38393 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brian L Foster Kanako J Nagatomo Francisco H Nociti Hanson Fong Daisy Dunn Anne B Tran Wei Wang Sonoko Narisawa Jose Luis Millán Martha J Somerman Central role of pyrophosphate in acellular cementum formation.
description	<h4>Background</h4>Inorganic 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.<h4>Results</h4>Excess 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.<h4>Conclusions</h4>Results 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.
format	article
author	Brian L Foster Kanako J Nagatomo Francisco H Nociti Hanson Fong Daisy Dunn Anne B Tran Wei Wang Sonoko Narisawa Jose Luis Millán Martha J Somerman
author_facet	Brian L Foster Kanako J Nagatomo Francisco H Nociti Hanson Fong Daisy Dunn Anne B Tran Wei Wang Sonoko Narisawa Jose Luis Millán Martha J Somerman
author_sort	Brian L Foster
title	Central role of pyrophosphate in acellular cementum formation.
title_short	Central role of pyrophosphate in acellular cementum formation.
title_full	Central role of pyrophosphate in acellular cementum formation.
title_fullStr	Central role of pyrophosphate in acellular cementum formation.
title_full_unstemmed	Central role of pyrophosphate in acellular cementum formation.
title_sort	central role of pyrophosphate in acellular cementum formation.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/12d0fba9e7b44068af999f54a6b83b2c
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Central role of pyrophosphate in acellular cementum formation.

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