Retinol deprivation partially rescues the skeletal mineralization defects of Phex-deficient Hyp mice.
Standard
Retinol deprivation partially rescues the skeletal mineralization defects of Phex-deficient Hyp mice. / Seitz, Sebastian; Rendenbach, Carsten; Barvencik, Florian; Streichert, Thomas; Jeschke, Anke; Schulze, Jochen; Amling, Michael; Schinke, Thorsten.
in: BONE, Jahrgang 53, Nr. 1, 1, 2013, S. 231-238.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Retinol deprivation partially rescues the skeletal mineralization defects of Phex-deficient Hyp mice.
AU - Seitz, Sebastian
AU - Rendenbach, Carsten
AU - Barvencik, Florian
AU - Streichert, Thomas
AU - Jeschke, Anke
AU - Schulze, Jochen
AU - Amling, Michael
AU - Schinke, Thorsten
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2013
Y1 - 2013
N2 - X-linked hypophosphatemic rickets (XLH) is a genetic disorder caused by mutational inactivation of the PHEX gene, encoding a transmembrane endopeptidase expressed in osteoblasts. Since several experiments involving Phex-deficient Hyp mice have demonstrated that an increased expression of Fgf23 in osteoblasts is causative for the renal phosphate loss characteristic of XLH, we performed genome-wide expression analysis to compare differentiated osteoblasts from wildtype and Hyp mice. Here we did not only observe the expected increase of Fgf23 expression in the latter ones, but also a differential expression of genes that are either induced by or involved in retinoic acid signaling, which led us to analyze whether dietary retinol deprivation would influence the phenotype of Hyp mice. Unexpectedly, feeding a retinol-free diet resulted in a partial rescue of the growth plate and bone mineralization defects in 6 weeks old Hyp mice. When we fed the same diet for 24 weeks the amount of non-mineralized bone matrix (osteoid) was reduced by more than 70%, although phosphate homeostasis was unaffected. In contrast, a dietary normalization of serum phosphate levels in Hyp mice reduced the osteoid amount by less than 30%, thereby demonstrating a previously unknown impact of retinol on the cell-autonomous mineralization defect of Phex-deficient osteoblasts.
AB - X-linked hypophosphatemic rickets (XLH) is a genetic disorder caused by mutational inactivation of the PHEX gene, encoding a transmembrane endopeptidase expressed in osteoblasts. Since several experiments involving Phex-deficient Hyp mice have demonstrated that an increased expression of Fgf23 in osteoblasts is causative for the renal phosphate loss characteristic of XLH, we performed genome-wide expression analysis to compare differentiated osteoblasts from wildtype and Hyp mice. Here we did not only observe the expected increase of Fgf23 expression in the latter ones, but also a differential expression of genes that are either induced by or involved in retinoic acid signaling, which led us to analyze whether dietary retinol deprivation would influence the phenotype of Hyp mice. Unexpectedly, feeding a retinol-free diet resulted in a partial rescue of the growth plate and bone mineralization defects in 6 weeks old Hyp mice. When we fed the same diet for 24 weeks the amount of non-mineralized bone matrix (osteoid) was reduced by more than 70%, although phosphate homeostasis was unaffected. In contrast, a dietary normalization of serum phosphate levels in Hyp mice reduced the osteoid amount by less than 30%, thereby demonstrating a previously unknown impact of retinol on the cell-autonomous mineralization defect of Phex-deficient osteoblasts.
KW - Animals
KW - Base Sequence
KW - Calcification, Physiologic
KW - DNA Primers
KW - Diet
KW - Familial Hypophosphatemic Rickets
KW - Fibroblast Growth Factors
KW - Genetic Diseases, X-Linked
KW - Mice
KW - PHEX Phosphate Regulating Neutral Endopeptidase
KW - Polymerase Chain Reaction
KW - Vitamin A
U2 - 10.1016/j.bone.2012.12.009
DO - 10.1016/j.bone.2012.12.009
M3 - SCORING: Journal article
C2 - 23266491
VL - 53
SP - 231
EP - 238
JO - BONE
JF - BONE
SN - 8756-3282
IS - 1
M1 - 1
ER -