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bioRxiv · 10.64898/2025.12.23.696208

Cell-based calcification assays - magnesium overrules calcium phosphate saturation in overall outcome

Morgan, A.·Hasberg, C.·Winkler, C.·Dzhanaev, R.·Graeber, S.·Reicher, L.·Gorgels, A.·Goettsch, C.·Jahnen-Dechent, W.
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Abstract

Soft tissue calcification, a common cause of cardiovascular mortality in conditions like chronic kidney disease (CKD), is influenced by magnesium (Mg). However, the exact mechanism, whether extracellular chemistry-mediated or cell-mediated, remains unclear. Here we focused on the extracellular milieu. Using fluorescence-labelled fetuin-A and a live imaging platform, we found that Mg reduced spontaneous mineral precipitation by stabilizing calcium and phosphate as colloidal protein-mineral particles (CPP) in calcification media containing up to 10 mM calcium and phosphate. Addition of 1.25-5 mM Mg progressively stabilized the protein-mineral particles in the fluid phase, increasing calcification. Dynamic light scattering revealed smaller and more numerous CPP at up to 4 mM Mg. At 10 mM Mg, no calcification occurred even with 10 mM added calcium and phosphate. This suggested a critical Mg concentration range in supersaturated calcification media, where Mg paradoxically enhanced calcification by stabilizing mineral precursors and increasing their availability. These findings demonstrate Mgs dual role: an inhibitor of protein-mineral complex aggregation at high concentrations and a facilitator of mineral availability from colloidal protein-mineral phases at concentrations up to about 5 mM Mg. This highlights the role of Mg in providing highly dynamic, mineral-rich, stable protein-mineral complexes driving matrix calcification, yet preventing mineral precipitation.

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Morgan, A., Hasberg, C., Winkler, C., Dzhanaev, R., Graeber, S., Reicher, L., Gorgels, A., Goettsch, C., Jahnen-Dechent, W.. 2025-12-25. Cell-based calcification assays - magnesium overrules calcium phosphate saturation in overall outcome. https://doi.org/10.64898/2025.12.23.696208

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