AQUA 2024

August 26 - 30, 2024

Copenhagen, Denmark

BONE MATRIX FORMATION IS INDEPENDENT FROM BONE MINERALISATION; STUDIES ON FARMED ATLANTIC SALMON AND ZEBRAFISH

P. Eckhard Witten*, Per Gunnar Fjelldal, Silvia Cotti, Wolfgang Koppe, Thea Morken, Lucia Drábiková

 

Ghent University, Biology Department, Ledeganckstraat 35, 9000 Ghent, Belgium peckhardwitten@aol.com

 

 



A series of studies on farmed Atlantic salmon and the zebrafish model clearly show bone matrix formation and matrix mineralisation as separated processes (1-3). This has consequence for the diagnosis of skeletal malformation and for the evaluation of the consequences of phosphorus deficiency. In salmon and zebrafish matrix formation and mineralisation become uncoupled if the animals receive a low phosphorus (P) diet. Osteoblasts continue bone matrix formation under conditions of low dietary P intake. Likewise the formation of non mineralised scales matrix continues. A limited low P period does not cause an increase of vertebral column malformations (1-3). The no-mineralised bone matrix that is produced during low P intake can fully mineralise if animals receive again a P-sufficient diet (2,3).

Low-P dietary intake, reduces plasma P levels in salmon by 50% but osteoblasts continue regular bone matrix formation. Ultrahigh resolution synchrotron tomography scans show that reduced P intake in zebrafish even increases the amount of non-mineralised bone matrix (Fig. 1) (1). Delayed bone matrix mineralisation has no effect on the expression of osteoblast key genes. In salmon vertebral bodies, the expression of bgp, col1a1, enpp1, entpd5, and opn remains unaltered. Only plasma fgf23, coding for a hormone that decreases renal P re-absorption, is down-regulated under low P conditions (4), indicating higher P retention. If zebrafish and salmon return to a P-sufficient diet, the non-mineralised bone matrix mineralises. Mineralisation does not resume in the vicinity of osteoblasts but far away from the cells connected to the last mineralised matrix (2). This suggests that osteoblasts produce a "mineralisation-ready" matrix but the actual process of matrix mineralisation is cell-independent. Bone matrix mineralisation arguably depends on the availability of plasma P and possibly, as recently suggested, on the composition of the collagenous matrix (5).

A better understanding of the effect of low, regular and high dietary P intake on bone cells and  on the growth and the mineralisation of the skeleton can help to optimise P levels in fish diets.

1. Cotti et al. (2020) More Bone with Less Minerals. Int. J Mol. Sci., 21, 5429.

2. Witten et al. (2019) Journal of Experimental Biology 222.

3. Drábiková et al. (2022) Aquaculture 559, 738430.

4. Drábiková et al. (2023). Biomolecules 13, 663.

5. van der Meijden et. al. (2023). Adv. Funct. Mater. 2212339.