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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Modulation of Phosphate/Pyrophosphate Metabolism to Regenerate the Periodontium: A Novel In Vivo Approach

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Author(s):
Rodrigues, Thaisangela L. [1] ; Nagatomo, Kanako J. [2] ; Foster, Brian L. ; Nociti, Jr., Francisco H. [1, 3] ; Somerman, Martha J. [3]
Total Authors: 5
Affiliation:
[1] Univ Estadual Campinas, Dept Prosthodont & Periodont, Div Periodont, Sch Dent, Piracicaba, SP - Brazil
[2] Univ Washington, Sch Dent, Dept Periodont, Seattle, WA 98195 - USA
[3] NIAMSD, NIH, Bethesda, MD 20892 - USA
Total Affiliations: 3
Document type: Journal article
Source: Journal of Periodontology; v. 82, n. 12, p. 1757-1766, DEC 2011.
Web of Science Citations: 16
Abstract

Background: The developing periodontium is sensitive to local levels of inorganic phosphate (P(i)) and inorganic pyrophosphate (PP(i)) as demonstrated by cementum phenotypes resulting from the loss of function of protein regulators of P(i)/PP(i) homeostasis. The progressive ankylosis protein (ANK) regulates the transport of PP(i), and progressive ankylosis gene (Ank) and knock-out (KO) mice feature a rapidly forming and thick cementum. We hypothesized that, besides affecting cementum formation, decreased extracellular PP(i) levels in Ank KO mice would also impact cementum regeneration. Methods: Periodontal fenestration defects (approximate to 2 mm in length, 1 mm in width, and 0.5 mm in depth) were created on buccal aspects of mandibular molars in Ank KO and wild-type (WT) mice. Mandibles were harvested at 15 and 30 days post-surgery for histology, histomorphometry, evaluation of in vivo fluorochrome labeling, and immunohistochemistry (IHC) for proteins including bone sialoprotein (BSP), osteopontin (OPN), dentin matrix protein 1 (DMP1), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). Results: A greater amount of new cementum was observed in Ank KO mice at 15 and 30 days post-surgery (P < 0.05), which was confirmed by fluorochrome labeling showing a higher new cementum appositional activity in defect areas in Ank KO mice versus controls. At days 15 and 30 during healing, regenerating cementum and associated cells in Ank KO samples recapitulated expression patterns mapped during development, including limited BSP and positive OPN and DMP1 in the cementum matrix as well as elevated NPP1 in cemento-blasts. Conclusions: Within the limits of the study, these findings suggest that reduced local levels of PP, could promote increased cementum regeneration. Therefore, the local modulation of P(i)/PP(i) may be a potential therapeutic approach for achieving improved cementum regeneration. J Periodontol 2011;82: 1757-1766. (AU)

FAPESP's process: 08/00534-7 - Regulation of dentin-pulp and periodontal ligament cells in healthy individuals and with hypophosphatasia
Grantee:Márcio Zaffalon Casati
Support Opportunities: Regular Research Grants