Lian J B, Boivin G, Patterson-Allen P, Grynpas M, Walzer C
Calcif Tissue Int. 1983 Jul;35(4-5):555-61. doi: 10.1007/BF02405093.
gamma-Carboxyglutamate (Gla), a calcium binding amino acid whose synthesis depends on vitamin K, has been found in association with pathologic calcifications. It is of interest therefore to examine the role of Gla-containing proteins in the formation of nonskeletal mineralized tissues. Calcergy and calciphylaxis, experimentally induced models of pathologic calcification, offer the opportunity to study the formation of mineral deposits in the absence of an endochondral sequence of bone formation. Before induction of subcutaneous calcinosis by topical treatment with the direct calcergen, KMnO4, or by challenging dihydrotachysterol-sensitized animals with FeCl2, control specimens contain no gamma-carboxyglutamic acid. With the initial formation of cytoplasmic vesicles, calcium content of the tissues increases and Gla is detected. Gla levels are further elevated with the appearance of poorly crystalline apatite-like crystallites. Origin of protein bound Gla was established by positive identification of osteocalcin by radioimmunoassay. Gla and osteocalcin appear concomitant with the earliest mineral deposits observed by electron microscopy and micro X-ray analysis. The formation of organized extracellular pattern by X-ray diffraction allowed sufficient mineral accumulation for detection with calcium, Gla, and osteocalcin increasing allowed sufficient mineral accumulation for detection of an apatite-like pattern by X-ray diffraction with calcium, Gla, and osteocalcin increasing proportionately as mineral is deposited.
γ-羧基谷氨酸（Gla）是一种钙结合氨基酸，其合成依赖于维生素K，已被发现与病理性钙化有关。因此，研究含Gla蛋白在非骨骼矿化组织形成中的作用具有重要意义。钙能沉着症和钙化防御是病理性钙化的实验诱导模型，为研究在没有软骨内骨形成序列的情况下矿物质沉积的形成提供了机会。在用直接钙诱导剂高锰酸钾进行局部治疗诱导皮下钙化之前，或者在用FeCl2对二氢速甾醇致敏的动物进行激发之前，对照标本中不含γ-羧基谷氨酸。随着细胞质小泡的最初形成，组织中的钙含量增加，并检测到Gla。随着类磷灰石微晶的出现，Gla水平进一步升高。通过放射免疫测定法对骨钙素进行阳性鉴定，确定了与蛋白质结合的Gla的来源。Gla和骨钙素与通过电子显微镜和微X射线分析观察到的最早矿物质沉积同时出现。通过X射线衍射形成有组织的细胞外模式，允许足够的矿物质积累以便用钙进行检测，随着矿物质沉积，Gla和骨钙素增加，允许足够的矿物质积累以便通过X射线衍射检测类磷灰石模式，钙、Gla和骨钙素成比例增加。
