Young John D, Martel Jan, Young David, Young Andrew, Hung Chin-Ming, Young Lena, Chao Ying-Jie, Young James, Wu Cheng-Yeu
Laboratory of Nanomaterials, Chang Gung University, Gueishan, Taiwan, Republic of China.
PLoS One. 2009;4(5):e5421. doi: 10.1371/journal.pone.0005421. Epub 2009 May 1.
Calcium and apatite granulations are demonstrated here to form in both human and fetal bovine serum in response to the simple addition of either calcium or phosphate, or a combination of both. These granulations are shown to represent precipitating complexes of protein and hydroxyapatite (HAP) that display marked pleomorphism, appearing as round, laminated particles, spindles, and films. These same complexes can be found in normal untreated serum, albeit at much lower amounts, and appear to result from the progressive binding of serum proteins with apatite until reaching saturation, upon which the mineralo-protein complexes precipitate. Chemically and morphologically, these complexes are virtually identical to the so-called nanobacteria (NB) implicated in numerous diseases and considered unusual for their small size, pleomorphism, and the presence of HAP. Like NB, serum granulations can seed particles upon transfer to serum-free medium, and their main protein constituents include albumin, complement components 3 and 4A, fetuin-A, and apolipoproteins A1 and B100, as well as other calcium and apatite binding proteins found in the serum. However, these serum mineralo-protein complexes are formed from the direct chemical binding of inorganic and organic phases, bypassing the need for any biological processes, including the long cultivation in cell culture conditions deemed necessary for the demonstration of NB. Thus, these serum granulations may result from physiologically inherent processes that become amplified with calcium phosphate loading or when subjected to culturing in medium. They may be viewed as simple mineralo-protein complexes formed from the deployment of calcification-inhibitory pathways used by the body to cope with excess calcium phosphate so as to prevent unwarranted calcification. Rather than representing novel pathophysiological mechanisms or exotic lifeforms, these results indicate that the entities described earlier as NB most likely originate from calcium and apatite binding factors in the serum, presumably calcification inhibitors, that upon saturation, form seeds for HAP deposition and growth. These calcium granulations are similar to those found in organisms throughout nature and may represent the products of more general calcium regulation pathways involved in the control of calcium storage, retrieval, tissue deposition, and disposal.
在此证明，在人血清和胎牛血清中，仅添加钙、磷酸盐或两者的组合，即可形成钙和磷灰石颗粒。这些颗粒显示为蛋白质与羟基磷灰石（HAP）的沉淀复合物，呈现出明显的多形性，表现为圆形、层状颗粒、纺锤体和薄膜。这些相同的复合物也可在未经处理的正常血清中发现，尽管含量要低得多，并且似乎是血清蛋白与磷灰石逐渐结合直至达到饱和的结果，此时矿质蛋白复合物沉淀。从化学和形态学上看，这些复合物与涉及多种疾病的所谓纳米细菌（NB）几乎相同，它们因其体积小、多形性和存在HAP而被认为不同寻常。与NB一样，血清颗粒转移到无血清培养基中时可形成颗粒，其主要蛋白质成分包括白蛋白、补体成分3和4A、胎球蛋白-A、载脂蛋白A1和B100，以及血清中发现的其他钙和磷灰石结合蛋白。然而，这些血清矿质蛋白复合物是由无机相和有机相的直接化学结合形成的，无需任何生物过程，包括在细胞培养条件下长时间培养，而这被认为是证明NB所必需的。因此，这些血清颗粒可能是生理固有过程的结果，在磷酸钙负荷增加或在培养基中培养时会被放大。它们可被视为由身体用于应对过量磷酸钙以防止不必要钙化的钙化抑制途径形成的简单矿质蛋白复合物。这些结果表明，先前描述为NB的实体很可能源自血清中的钙和磷灰石结合因子，大概是钙化抑制剂，它们在饱和时形成HAP沉积和生长的种子，而不是代表新的病理生理机制或奇异的生命形式。这些钙颗粒与自然界中生物体中发现的颗粒相似，可能代表参与钙储存、回收利用、组织沉积和处理控制的更普遍钙调节途径的产物。
