PUBLICATION

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

Authors
Cotti, S., Di Biagio, C., Huysseune, A., Koppe, W., Forlino, A., Witten, P.E.
ID
ZDB-PUB-240724-13
Date
2024
Source
JBMR plus   8: ziae081ziae081 (Journal)
Registered Authors
Cotti, Silvia, Forlino, Antonella, Huysseune, Ann, Witten, P. Eckhard
Keywords
analysis/quantitation of bone, animal models, collagen, matrix mineralization, osteoblasts
MeSH Terms
none
PubMed
39045128 Full text @ JBMR Plus
Abstract
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.
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