Increased Col10a1 expression is not causative for the phenotype of Phex-deficient Hyp mice

TY - JOUR

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 -