Biologische Mineralisation vs. Pathologische Kalzifizierung – die Rolle des Mineral-Chaperons Fetuin-A

Zusammenfassung

Die Mineralien Kalzium und Phosphat sind für den Zellstoffwechsel aller lebenden Organismen unverzichtbar. Beide Ionen kommen in biologischen Flüssigkeiten normalerweise in millimolaren Konzentrationen vor. Dies führt zu einem Löslichkeits- und Transportproblem, da Kalziumphosphate in Wasser kaum löslich sind und leicht aus übersättigten Lösungen ausfallen. Mineral-Chaperone stabilisieren Mineral als Kolloid und ermöglichen so den Transport und die Clearance nominell übersättigter Mineral-Lösungen. Am Beispiel des Plasmaproteins Fetuin-A erklären wir die Rolle systemischer Mineral-Chaperone, insbesondere bei gestörtem Mineralstoffwechsel. Wir beschreiben den Stoffwechsel kolloidaler Protein-Mineralkomplexen, die in Anlehnung an Lipoprotein-Partikel Calciprotein-Partikel, kurz CPP genannt werden. Wir behandeln die Rolle von CPP bei der physiologischen Knochenbildung und der pathologischen Kalzifizierung. Wir nennen wesentliche Regulatoren von Ossifizierung und Kalzifizierung auf Ebene der Gene, Proteine und Metaboliten. Zuletzt erörtern wir mögliche Therapien von Kalzifizierung anhand eines hierarchischen Modells von mineralinduziertem Stress.

Abstract

The minerals calcium and phosphate are essential for cell metabolism in all living organisms. Both ions normally occur in biological fluids in millimolar concentrations. This leads to a solubility and transport problem, as calcium phosphates are poorly soluble in water and readily precipitate from supersaturated solutions. Mineral chaperones stabilize mineral as a colloid, allowing transport and clearance of nominally supersaturated mineral solutions. Using the plasma protein fetuin-A as an example, we explain the role of systemic mineral chaperones, particularly in the presence of impaired mineral metabolism. We describe the metabolism of colloidal protein-mineral complexes, which we have named calciprotein particles, or CPP, in reference to lipoprotein particles. We address the role of CPP in physiological bone formation and pathological calcification. We name key regulators of ossification and calcification at the gene, protein, and metabolite levels. Last, we discuss potential therapies of calcification using a hierarchical model of mineral-induced stress.

Schlüsselwörter

Biomineralisation - Kalzifizierung - Mineral Chaperone - Heterotope Ossifikation - Fetuin-A

Key words

Biomineralization - Calcification - Mineral Chaperones - Heterotopic Ossification - Fetuin-A

Publikationsverlauf

Eingereicht: 06. September 2022

Angenommen: 15. Oktober 2022

Artikel online veröffentlicht:
14. Dezember 2022

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