权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The structure of amorphous calcium phosphate, a key intermediate in skeletal calcification

骨骼钙化关键中间体无定形磷酸钙的结构

基本信息

批准号：
EP/E006337/1
负责人：
Gavin Mountjoy
金额：
$ 9.28万
依托单位：
University of Kent
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2006
资助国家：
英国
起止时间：
2006 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FE006337%2F1
关键词：
structure amorphous calcium phosphate key

项目摘要

This proposal will make a key advance in our understanding of the process of bone growth. Of course, bone growth is very important to humans as bones form the skeleton, which provides mechanical support. In fact bones are a distinguishing feature of all animals which are vertebrates. The ability to make bones developed during evolution and there is evidence that it already existed 500Million years ago. Our bones are made of a mixture of a protein called collagen and a mineral called hydroxyapatite. Hydroxyapatite is a calcium phosphate compound (hence the importance of calcium in the diet for healthy bones). Minerals like hydroxyapatite are normally made in geological processes, and similar processes can be used to make synthetic minerals in industry. However, the body uses a different approach to make the bone mineral hydroxyapatite.Most people think that bone growth is restricted to the early stages of life. Actually, during our whole lives bones are constantly remodelled by absorption and reformation processes. (When these processes malfunction illnesses can result, such as osteoporosis.) These processes necessarily involve the circulation of calcium and phosphate within the body, and these ions are present in the body fluid which circulates among cells. Scientists already understand a lot about bone growth. During bone growth, calcium and phosphate ions from the body fluid are deposited at a site where new bone is required. These ions precipitate to form a solid calcium phosphate compound. Interestingly, the first compound formed is not the bone mineral hydroxyapatite. Hydroxyapatite is formed by subsequent reactions from the first compound.Surprisingly, the structure of the first calcium phosphate compound formed is still unknown, over 50 years after it was discovered. It was given the name amorphous calcium phosphate because it is not crystalline (amorphous means non-crystalline). Since it is not crystalline, it's structure cannot be identified using standard methods such as crystallography. Without knowing the structure of this compound, scientists are unable to describe the very early stage of bone formation, and hence a key piece of knowledge is missing.This proposal will provide the missing knowledge by applying special techniques to identify the structure of amorphous calcium phosphate. These techniques are ones which scientists have developed to study glasses, such as window glass, which are also non-crystalline. The techniques include special diffraction experiments (similar to crystallography) and computer modelling. These techniques have successfully revealed the structure of glasses, but they are less often applied to amorphous materials in biology.Knowing the structure of amorphous calcium phosphate will improve our knowledge of bone growth. This will provide important benefits. Firstly, for our understanding of biology (including illnesses such as urinary stones). Secondly, for scientists who are making bioactive materials, which are designed to be implanted in the body and to mimic the body's own bone growth processes. Thirdly, for scientists who want to find alternative ways to make minerals (without using geological processes).

这一建议将在我们对骨骼生长过程的理解方面取得关键进展。当然，骨骼的生长对人类非常重要，因为骨骼形成了提供机械支持的骨骼。事实上，骨骼是所有脊椎动物的一个显著特征。制造骨骼的能力是在进化过程中发展起来的，有证据表明，它在5亿年前就已经存在了。我们的骨骼是由一种名为胶原蛋白的蛋白质和一种名为羟基磷灰石的矿物混合而成的。羟基磷灰石是一种磷酸钙化合物(因此钙在骨骼健康饮食中的重要性)。像羟基磷灰石这样的矿物通常是在地质过程中制造的，类似的过程也可以用来在工业上制造合成矿物。然而，人体使用了一种不同的方法来使骨骼矿物质羟基磷灰石。大多数人认为骨骼的生长仅限于生命的早期阶段。事实上，在我们的一生中，骨骼不断地被吸收和改造过程重塑。(当这些过程出现故障时，可能会导致疾病，如骨质疏松症。)这些过程必然涉及体内钙和磷的循环，而这些离子存在于在细胞之间循环的体液中。科学家们已经对骨骼生长有了很多了解。在骨骼生长过程中，体液中的钙和磷离子会沉积在需要新骨的部位。这些离子沉淀形成固体磷酸钙化合物。有趣的是，第一个形成的化合物并不是骨矿羟基磷灰石。羟基磷灰石是由第一个化合物经过后续反应形成的。令人惊讶的是，第一个形成的磷酸钙化合物的结构在被发现50多年后仍然未知。它之所以被命名为无定形磷酸钙，是因为它不是晶态的(非晶态意味着非晶态)。因为它不是结晶的，所以它的结构不能用结晶学等标准方法来鉴定。在不知道这种化合物的结构的情况下，科学家无法描述骨形成的非常早期阶段，因此缺少一项关键的知识。这一建议将通过应用特殊技术来确定无定形磷酸钙的结构来弥补缺少的知识。这些技术是科学家为了研究玻璃而开发的，比如窗户玻璃，它也是非晶态的。这些技术包括特殊的衍射实验(类似于结晶学)和计算机模拟。这些技术已经成功地揭示了玻璃的结构，但它们在生物学中较少应用于非晶态材料。了解非晶态磷酸钙的结构将提高我们对骨生长的了解。这将带来重要的好处。首先，为了我们对生物学(包括尿路结石等疾病)的了解。其次，对于正在制造生物活性材料的科学家来说，这种材料旨在植入人体内，并模拟人体自身的骨骼生长过程。第三，对于那些想要寻找替代方法来制造矿物(不使用地质过程)的科学家来说。