Matrix first, minerals later: fine-tuned dietary phosphate increases bone formation in zebrafish

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F24%3A10487165" target="_blank" >RIV/00216208:11310/24:10487165 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FoQbh~Yi30" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FoQbh~Yi30</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/jbmrpl/ziae081" target="_blank" >10.1093/jbmrpl/ziae081</a>

Result language

angličtina

Original language name

Matrix first, minerals later: fine-tuned dietary phosphate increases bone formation in zebrafish

Original language description

Bone matrix formation and mineralization are two closely related, yet separated processes. Matrix formation occurs first, mineralization is a second step strictly dependent on the dietary intake of calcium and phosphorus (P). However, mineralization is commonly used as diagnostic parameter for bone-related diseases. In this context, bone loss, often characterized as a condition with reduced bone mineral density, represents a major burden for human health, for which increased dietary mineral intake is generally recommended. Using a counterintuitive approach, we use a low-P diet followed by a sufficient-P intake to increase bone volume. We show in zebrafish by histology, qPCR, micro-CT, and enzyme histochemistry that a two-months period of reduced dietary P intake stimulates extensive formation of new bone matrix, associated with the upregulation of key genes required for both bone matrix formation and mineralization. The return to a P-sufficient diet initiates the mineralization of the abundant matrix previously deposited, thus resulting in a striking increase of the mineralized bone volume as proven at the level of the vertebral column, including vertebral bodies and arches. In summary, bone matrix formation is first stimulated with a low-P diet, and its mineralization is later triggered by a sufficient-P dietary intake. In zebrafish, the uncoupling of bone formation and mineralization by alternating low and sufficient dietary P intake significantly increases the bone volume without causing skeletal malformations or ectopic mineralization. A modification of this approach to stimulate bone formation, optimized for mammalian models, can possibly open opportunities to support treatments in patients that suffer from low bone mass. Bone loss, typically associated to bone fragility, represents a major burden for human health. Bone is constituted by an organic collagen scaffold undergoing mineralization. In physiological conditions, the ratio between mineral content and collagen matrix ensures optimal bone properties. An increased mineral amount compared to the deposited matrix results in bone loss and fragility. Stimulating the formation of new bone matrix prior its mineralization will increase the collagen scaffold volume, paving the way for increased bone volume upon mineral deposition. In this context, we show that in zebrafish reduced dietary phosphorus intake for a limited time stimulates the formation of large amounts of non-mineralized bone matrix. The newly formed bone matrix resumes mineralization upon sufficient dietary phosphorus intake, thus resulting in significantly increased mineralized bone volume. The modulation of phases of different dietary phosphorus intake, when optimized on mammalian models, has the potential to unlock new strategies in the treatment of bone diseases, as it could eventually help to increase the bone volume in patients without, or in addition to, pharmacological intervention.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10613 - Zoology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

JBMR plus

ISSN

2473-4039

e-ISSN

2473-4039

Volume of the periodical

8

Issue of the periodical within the volume

8

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

ziae081

UT code for WoS article

001274159200002

EID of the result in the Scopus database

2-s2.0-85199802338