English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Mutations in the human progressive ankylosis gene ( ANKH; Mus musculus ortholog Ank ) have been identified as cause for craniometaphyseal dysplasia (CMD), characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. We previously reported a knock-in (KI) mouse model ( Ank   KI/KI ) for CMD and showed transiently lower serum phosphate (Pi) as well as significantly higher mRNA levels of fibroblast growth factor 23 ( Fgf23 ) in  Ank   KI/KI  mice. FGF23 is secreted by bone and acts in kidney to promote Pi wasting which leads to lower serum Pi levels. Here, we examined whether increasing the Pi level can partially rescue the CMD-like skeletal phenotype by feeding  Ank   +/+  and  Ank   KI/KI  mice with high Pi (1.7 %) diet from birth for 6 weeks. We studied the Pi metabolism in  Ank   KI/KI  mice and CMD patients by examining the Pi regulators FGF23 and parathyroid hormone (PTH).    Results  High Pi diet did not correct CMD-like features, including massive jawbone, increased endosteal and periosteal perimeters and extensive trabeculation of femurs in  Ank   KI/KI  mice shown by computed microtomography (μCT). This unexpected negative result is, however, consistent with normal serum/plasma levels of the intact/active form of FGF23 and PTH in  Ank   KI/KI  mice and in CMD patients. In addition, FGF23 protein expression was unexpectedly normal in  Ank   KI/KI  femoral cortical bone as shown by immunohistochemistry despite increased mRNA levels for  Fgf23 . Renal expression of genes involved in the FGF23 bone-kidney axis, including  mFgfr1, mKlotho, mNpt2a, mCyp24a1 and m1αOHase,  were comparable between  Ank   +/+  and  Ank   KI/KI  mice as shown by quantitative real-time PCR. Different from normal FGF23 and PTH, serum 25-hydroxyvitamin D was significantly lower in  Ank   KI/KI  mice and vitamin D insufficiency was found in four out of seven CMD patients.    Conclusions  Our data suggests that FGF23 signaling and Pi metabolism are not significantly affected in CMD and transiently low Pi level is not a major contributor to CMD.

Dietary phosphate supplement does not rescue skeletal phenotype in a mouse model for craniometaphyseal dysplasia