Genetics of Sost/SOST in sclerosteosis and van Buchem disease animal models.
Genetics of Sost/SOST in sclerosteosis and van Buchem disease animal models.
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DOI：
10.1016/j.metabol.2017.10.005
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发表时间：
2017-10
期刊：
影响因子：
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通讯作者：
A. Sebastian;G. Loots
中科院分区：
文献类型：
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作者：
A. Sebastian;G. Loots
硬化症和货车-布赫姆病（VBD）是两种罕见的常染色体隐性遗传疾病，由成骨细胞过度活跃引起，其中进行性骨过度生长导致非常致密的骨、面部变形和颅神经卡压。硬化症是由SOST基因的功能缺失突变引起的，SOST基因编码一种分泌性糖蛋白，硬化素。VBD是由非编码缺失引起的，该缺失去除了骨中的aSOST特异性调节元件。在骨中，SOST主要由骨细胞表达，硬化蛋白通过抑制经典Wnt信号通路抑制骨形成。在这里，我们描述了如何在骨质疏松症和VBD患者的人类遗传学研究，结合转基因和基因敲除小鼠的产生，导致了更好地了解sclerostin在骨代谢中的作用。
Sclerosteosis and van Buchem disease (VBD) are two rare autosomal recessive disorders that results from osteoblast hyperactivity, in which progressive bone overgrowth leads to very dense bones, distortion of the face, and entrapment of cranial nerves. Sclerosteosis is caused by loss-of-function mutations in theSOSTgene which encodes a secreted glycoprotein, sclerostin. VBD is caused by a noncoding deletion that removes aSOST-specific regulatory element in bone. In bone,SOSTis expressed predominantly by osteocytes and sclerostin suppresses bone formation by inhibiting the canonical Wnt signaling pathway. Here we describe how human genetics studies in sclerosteosis and VBD patients, in combination with the generation of transgenic and knockout mice, has led to a better understanding of the role of sclerostin in bone metabolism.