RWTH Aachen University Clinics, Pauwelsstrasse 30, 52074 Aachen, Germany.
Circ Res. 2011 Jun 10;108(12):1494-509. doi: 10.1161/CIRCRESAHA.110.234260.
The final step of biomineralization is a chemical precipitation reaction that occurs spontaneously in supersaturated or metastable salt solutions. Genetic programs direct precursor cells into a mineralization-competent state in physiological bone formation (osteogenesis) and in pathological mineralization (ectopic mineralization or calcification). Therefore, all tissues not meant to mineralize must be actively protected against chance precipitation of mineral. Fetuin-A is a liver-derived blood protein that acts as a potent inhibitor of ectopic mineralization. Monomeric fetuin-A protein binds small clusters of calcium and phosphate. This interaction results in the formation of prenucleation cluster-laden fetuin-A monomers, calciprotein monomers, and considerably larger aggregates of protein and mineral calciprotein particles. Both monomeric and aggregate forms of fetuin-A mineral accrue acidic plasma protein including albumin, thus stabilizing supersaturated and metastable mineral ion solutions as colloids. Hence, fetuin-A is a mineral carrier protein and a systemic inhibitor of pathological mineralization complementing local inhibitors that act in a cell-restricted or tissue-restricted fashion. Fetuin-A deficiency is associated with soft tissue calcification in mice and humans.
生物矿化的最后一步是一个化学沉淀反应，在过饱和或亚稳盐溶液中自发发生。遗传程序将前体细胞引导到生理骨形成（成骨作用）和病理性矿化（异位矿化或钙化）中的矿化能力状态。因此，所有不打算矿化的组织都必须积极防止矿物质偶然沉淀。胎球蛋白-A 是一种肝脏来源的血液蛋白，可作为异位矿化的有效抑制剂。单体胎球蛋白-A 蛋白结合少量的钙和磷酸盐。这种相互作用导致前成核簇负载的胎球蛋白-A 单体、钙结合蛋白单体以及相当大的蛋白质和矿物质钙结合蛋白颗粒的聚集物的形成。胎球蛋白-A 的单体和聚集形式都会积累酸性血浆蛋白，包括白蛋白，从而稳定过饱和和亚稳矿物质离子溶液作为胶体。因此，胎球蛋白-A 是一种矿物质载体蛋白，也是系统性的病理性矿化抑制剂，补充了以细胞受限或组织受限方式发挥作用的局部抑制剂。胎球蛋白-A 缺乏与小鼠和人类的软组织钙化有关。
