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"Inhibition of mineralization in bones and teeth following ectopic expression of matrix Gla protein"

Matrix Gla Protein (MGP) inhibits mineralization of arteries and cartilage. To determine its mineral-inhibiting potential in hard tissues, MGP was ectopically expressed in bones and teeth of mice using an osteoblast/odontoblast-specific 2.3kb proximal promoter for type 1 collagen. Mandibles and long bones of Col1a1-Mgp mice and wild-type littermates were analyzed by Faxitron(TM) radiography, PIXImus(TM) dual-energy x-ray absorptiometry (DEXA) and micro-computed tomography (mu-CT). In addition, light microscopy (LM) and transmission electron microscopy (TEM) were performed. While bone and tooth extracellular matrices (ECMs) appeared normally established in Col1a1-Mgp mice, examination of the mineral phase by radiography, DEXA and mu-CT, together with histological mineral localization by LM after von Kossa staining of undecalcified tissue sections, and by TEM, revealed massive hypomineralization of bone and tooth ECMs. In the skeleton of Col1a1-Mgp mice, alveolar bone of the mandible was most heavily affected (compared to long bones), showing a 50% increase in the unmineralized osteoid volume compared to wild-type littermates. For teeth, mineralization was virtually absent in root dentin of both incisors and molars, and absent in molar cellular cementum, whereas crown dentin showed localized "breakthrough" areas of mineralization. Acellular cementum formation and mineralization was absent in the Col1a1-Mgp mice. Immunohistochemical staining of bone and tooth ECM proteins in Col1a1-Mgp mice showed variations in staining relative to wild-type tissues, with immunostaining generally restricted to areas of mineralization. In conclusion, these results confirm in vivo that ECM proteins can act as inhibitors of bone and tooth mineralization.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.82260
Date January 2004
CreatorsKaipatur, Neelambar
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Faculty of Dentistry.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 002201580, proquestno: AAIMR12471, Theses scanned by UMI/ProQuest.

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