Increased Col10a1 expression is not causative for the phenotype of Phex-deficient Hyp mice
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Increased Col10a1 expression is not causative for the phenotype of Phex-deficient Hyp mice. / Yorgan, Timur; Rendenbach, Carsten; Jeschke, Anke; Amling, Michael; Cheah, Kathryn S E; Schinke, Thorsten.
in: BIOCHEM BIOPH RES CO, Jahrgang 442, Nr. 3-4, 13.12.2013, S. 209-13.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Increased Col10a1 expression is not causative for the phenotype of Phex-deficient Hyp mice
AU - Yorgan, Timur
AU - Rendenbach, Carsten
AU - Jeschke, Anke
AU - Amling, Michael
AU - Cheah, Kathryn S E
AU - Schinke, Thorsten
N1 - Copyright © 2013 Elsevier Inc. All rights reserved.
PY - 2013/12/13
Y1 - 2013/12/13
N2 - X-linked hypophosphatemic rickets (XLHR) is a severe disorder of phosphate homeostasis and skeletal mineralization caused by mutations of PHEX, encoding a bone-specific endopeptidase. Phex-deficient Hyp mice have been extensively studied to understand the molecular bases of XLHR, and here it was found that Fgf23, encoding a major phosphaturic hormone, was transcriptionally activated in bone-forming osteoblasts. We and others could additionally show that Col10a1 expression is increased in Hyp osteoblasts and bones, thereby raising the possibility that ectopic production of type X collagen could contribute to the impaired mineralization of the Hyp bone matrix. Here we show that an additional deficiency of the Col10a1 gene does not overtly affect the skeletal phenotype of Hyp mice. More specifically, Col10a1-deficient Hyp mice displayed severe disturbances of skeletal growth, bone mass acquisition and bone matrix mineralization, and they were essentially indistinguishable from Hyp littermates. This was confirmed by non-decalcified histology and bone-specific histomorphometry quantifying all relevant parameters of growth plate maturation, trabecular bone architecture and osteoid accumulation. Taken together, our results show that increased Col10a1 expression in Phex-deficient osteoblasts is not a major cause of the XLHR phenotype, which was an important issue to address based on the previous findings.
AB - X-linked hypophosphatemic rickets (XLHR) is a severe disorder of phosphate homeostasis and skeletal mineralization caused by mutations of PHEX, encoding a bone-specific endopeptidase. Phex-deficient Hyp mice have been extensively studied to understand the molecular bases of XLHR, and here it was found that Fgf23, encoding a major phosphaturic hormone, was transcriptionally activated in bone-forming osteoblasts. We and others could additionally show that Col10a1 expression is increased in Hyp osteoblasts and bones, thereby raising the possibility that ectopic production of type X collagen could contribute to the impaired mineralization of the Hyp bone matrix. Here we show that an additional deficiency of the Col10a1 gene does not overtly affect the skeletal phenotype of Hyp mice. More specifically, Col10a1-deficient Hyp mice displayed severe disturbances of skeletal growth, bone mass acquisition and bone matrix mineralization, and they were essentially indistinguishable from Hyp littermates. This was confirmed by non-decalcified histology and bone-specific histomorphometry quantifying all relevant parameters of growth plate maturation, trabecular bone architecture and osteoid accumulation. Taken together, our results show that increased Col10a1 expression in Phex-deficient osteoblasts is not a major cause of the XLHR phenotype, which was an important issue to address based on the previous findings.
KW - Animals
KW - Bone and Bones
KW - Collagen Type X
KW - Disease Models, Animal
KW - Familial Hypophosphatemic Rickets
KW - Gene Expression
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Mutant Strains
KW - Muscle, Skeletal
KW - Osteoblasts
KW - Osteomalacia
KW - PHEX Phosphate Regulating Neutral Endopeptidase
U2 - 10.1016/j.bbrc.2013.11.033
DO - 10.1016/j.bbrc.2013.11.033
M3 - SCORING: Journal article
C2 - 24269824
VL - 442
SP - 209
EP - 213
JO - BIOCHEM BIOPH RES CO
JF - BIOCHEM BIOPH RES CO
SN - 0006-291X
IS - 3-4
ER -