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Calcif Tissue Int. 2013 Oct;93(4):355-64. doi: 10.1007/s00223-012-9690-6. Epub 2013 Jan 1.

The role of fetuin-A in physiological and pathological mineralization.

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Helmholtz Institute for Biomedical Engineering, Biointerface Group, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.


Mineralization in higher vertebrates is restricted to bones and teeth. Pathological calcification is mostly known in vasculature but can basically affect all soft tissues. Simply put, tissue mineralization occurs through the interplay of three key determinants: extracellular matrix suitable for mineralization, extracellular levels of inorganic phosphate and calcium, and the levels of mineralization inhibitors that may be expressed systemically or locally. In this article we describe the role of a prototypic systemic inhibitor protein of mineralization, the hepatic plasma protein α2-Heremans-Schmid glycoprotein/fetuin-A. Fetuin-A mediates the formation of stable colloidal mineral-protein complexes called calciprotein particles (CPPs). Thus, fetuin-A is important in the stabilization and clearance of amorphous mineral precursor phases. Efficient clearance of CPPs and, thus, of excess mineral from circulation prevents local buildup of mineral and calcification of soft tissue. Besides calcium phosphate binding, fetuin-A also acts as a carrier for lipids, which may influence calcification, inflammation, and apoptosis. Fetuin-A-deficient (Ahsg(-/-)) mice show impaired growth of their long bones and premature growth plate closure. We posit that the absence of fetuin-A in the growth plate causes simultaneous lack of calcification inhibition and excess lipid hormone signaling, leading to premature growth plate mineralization and shortened long bones. This suggests that fetuin-A regulates endochondral ossification through mineralization inhibition and lipid (hormone) binding.

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