Abstract：
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 the SOST gene which encodes a secreted glycoprotein, sclerostin. VBD is caused by a noncoding deletion that removes a SOST-specific regulatory element in bone. In bone, SOST is 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.
摘要：
硬化病和范布赫姆病（VBD）是两种罕见的常染色体隐性遗传疾病，由成骨细胞多动症引起，其中进行性骨骼过度生长导致非常致密的骨骼，扭曲的脸，和脑神经的压迫。硬化是由SOST基因的功能缺失突变引起的，SOST基因编码分泌的糖蛋白，硬化蛋白.VBD是由去除了骨中SOST特异性调控元件的非编码缺失引起的。在骨头里，SOST主要由骨细胞表达，硬化蛋白通过抑制经典的Wnt信号通路抑制骨形成。在这里，我们描述了如何在硬化性和VBD患者中进行人类遗传学研究，结合转基因和基因敲除小鼠的产生，已经导致了对骨代谢中硬化蛋白的作用有了更好的理解。
