Ablation of systemic phosphate-regulating gene fibroblast growth factor 23 (Fgf23) compromises the dentoalveolar complex

E. Y. Chu, H. Fong, F. A. Blethen, K. A. Tompkins, B. L. Foster, K. D. Yeh, K. J. Nagatomo, D. Matsa-Dunn, D. Sitara, B. Lanske, R. B. Rutherford, M. J. Somerman

Research output: Contribution to journalArticle

Abstract

Fibroblast growth factor-23 (FGF23) is a hormone that modulates circulating phosphate (Pi) levels by controlling Pi reabsorption from the kidneys. When FGF23 levels are deficient, as in tumoral calcinosis patients, hyperphosphatemia ensues. We show here in a murine model that Fgf23 ablation disrupted morphology and protein expression within the dentoalveolar complex. Ectopic matrix formation in pulp chambers, odontoblast layer disruption, narrowing of periodontal ligament space, and alteration of cementum structure were observed in histological and electronmicroscopy sections. Because serum Pi levels are dramatically elevated in Fgf23-/-, we assayed for apoptosis and expression of members from the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, both of which are sensitive to elevated Pi in vitro. Unlike X-linked hypophosphatemic (Hyp) and wild-type (WT) specimens, numerous apoptotic osteocytes and osteoblasts were detected in Fgf23-/- specimens. Further, in comparison to Hyp and WT samples, decreased bone sialoprotein and elevated dentin matrix protein-1 protein levels were observed in cementum of Fgf23-/- mice. Additional dentin-associated proteins, such as dentin sialoprotein and dentin phosphoprotein, exhibited altered localization in both Fgf23-/- and Hyp samples. Based on these results, we propose that FGF23 and (Pi) homeostasis play a significant role in maintenance of the dentoalveolar complex.

Original languageEnglish (US)
Pages (from-to)1214-1226
Number of pages13
JournalAnatomical Record
Volume293
Issue number7
DOIs
StatePublished - Jul 2010

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Keywords

  • Fibroblast growth factor 23 (FGF23)
  • Phex
  • Phosphate metabolism
  • Tooth development

ASJC Scopus subject areas

  • Anatomy
  • Biotechnology
  • Histology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Chu, E. Y., Fong, H., Blethen, F. A., Tompkins, K. A., Foster, B. L., Yeh, K. D., Nagatomo, K. J., Matsa-Dunn, D., Sitara, D., Lanske, B., Rutherford, R. B., & Somerman, M. J. (2010). Ablation of systemic phosphate-regulating gene fibroblast growth factor 23 (Fgf23) compromises the dentoalveolar complex. Anatomical Record, 293(7), 1214-1226. https://doi.org/10.1002/ar.21152