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

Autor:	Cotti S; Biology Department, Evolutionary Developmental Biology, Ghent University, 9000 Gent, Belgium.; Department of Molecular Medicine, Biochemistry Unit, University of Pavia, 27100 Pavia, Italy., Di Biagio C; Biology Department, Evolutionary Developmental Biology, Ghent University, 9000 Gent, Belgium.; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy., Huysseune A; Biology Department, Evolutionary Developmental Biology, Ghent University, 9000 Gent, Belgium.; Department of Zoology, Charles University, 12800 Prague, Czech Republic., Koppe W; SimplyFish AS, 4011 Stavanger, Norway., Forlino A; Department of Molecular Medicine, Biochemistry Unit, University of Pavia, 27100 Pavia, Italy., Witten PE; Biology Department, Evolutionary Developmental Biology, Ghent University, 9000 Gent, Belgium.
Jazyk:	angličtina
Zdroj:	JBMR plus [JBMR Plus] 2024 Jun 18; Vol. 8 (8), pp. ziae081. Date of Electronic Publication: 2024 Jun 18 (Print Publication: 2024).
DOI:	10.1093/jbmrpl/ziae081
Abstrakt:	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. Competing Interests: S.C., C.D.B., A.H., A.F., P.E.W.: nothing to disclose. W.K. was employed by the company SimplyFish AS. (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)
Databáze:	MEDLINE
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