Matrix vesicles: structure, composition, formation and function in calcification.
Matrix vesicles: structure, composition, formation and function in calcification.
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DOI：
10.2741/3887
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
R. Wuthier;G. Lipscomb
中科院分区：
文献类型：
--
作者：
R. Wuthier;G. Lipscomb
基质囊泡（MV）在软骨内骨形成过程中诱导钙化。综述了分子筛的结构、组成和功能分析的实验方法。详细介绍了MV蛋白、酶、受体、转运蛋白、调节蛋白、脂质和电解质。MV的形成被认为是从结构和生物化学的角度。Ca（2+）和H（+）的共聚焦成像用于描绘活的软骨细胞如何形成MV。生物化学研究表明，协调的线粒体Ca（2+）和Pi代谢产生含有无定形磷酸钙，磷脂酰丝氨酸和膜联蛋白A5的成核复合物（NC）的MV-所有矿物成核机制的关键。重构的NC和建模与单层囊泡揭示了NC如何转化为磷酸八钙，调节Mg（2+），Zn（2+）和膜联蛋白A5。囊内矿物质外渗由磷脂酶和组织非特异性碱性磷酸酶（TNAP）介导。在囊外基质中，软骨胶原和TNAP（其破坏抑制性PPi）以及降解蛋白聚糖的金属蛋白酶增强了羟基磷灰石晶体的增殖。其他蛋白质也调节矿物质的形成。本文综述了TNAP、NPP 1、ANK、PHOSPHO 1和Annexin A5单基因和多基因敲除的最新研究结果。
Matrix vesicles (MVs) induce calcification during endochondral bone formation. Experimental methods for structural, compositional, and functional analysis of MVs are reviewed. MV proteins, enzymes, receptors, transporters, regulators, lipids and electrolytes are detailed. MV formation is considered from both structural and biochemical perspectives. Confocal imaging of Ca(2+) and H(+) were used to depict how living chondrocytes form MVs. Biochemical studies revealed that coordinated mitochondrial Ca(2+) and Pi metabolism produce MVs containing a nucleational complex (NC) of amorphous calcium phosphate, phosphatidylserine and annexin A5--all critical to the mechanism of mineral nucleation. Reconstitution of the NC and modeling with unilamellar vesicles reveal how the NC transforms into octacalcium phosphate, regulated by Mg(2+), Zn(2+) and annexin A5. Extravasation of intravesicular mineral is mediated by phospholipases and tissue-nonspecific alkaline phosphatase (TNAP). In the extravesicular matrix, hydroxyapatite crystal propagation is enhanced by cartilage collagens and TNAP, which destroys inhibitory PPi, and by metalloproteases that degrade proteoglycans. Other proteins also modulate mineral formation. Recent findings from single and multiple gene knockouts of TNAP, NPP1, ANK, PHOSPHO1, and Annexin A5 are reviewed.