Ablation of systemic phosphate-regulating gene fibroblast growth factor 23 (Fgf23) compromises the dentoalveolar complex.
Fibroblast growth factor-23 (FGF23) is a hormone that modulates circulating phosphate (P(i)) levels by controlling P(i) 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 electron microscopy sections. Because serum P(i) 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 P(i) 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 (P(i)) homeostasis play a significant role in maintenance of the dentoalveolar complex.
Chu
E Y
EY
Department of Periodontics, School of Dentistry, University of Washington, Seattle, Washington, USA.
Fong
H
H
Blethen
F A
FA
Tompkins
K A
KA
Foster
B L
BL
Yeh
K D
KD
Nagatomo
K J
KJ
Matsa-Dunn
D
D
Sitara
D
D
Lanske
B
B
Rutherford
R B
RB
Somerman
M J
MJ
D000539:Alveolar Process / Q000473:pathology*; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D053098:Familial Hypophosphatemic Rickets / Q000235:genetics / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics*; D040181:Genetic Diseases, X-Linked; D006801:Humans; D054559:Hyperphosphatemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D010011:Osteocytes / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism
D016326:Extracellular Matrix Proteins; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23