Genetics of Sost/SOST in sclerosteosis and van Buchem disease animal models.

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.

• Authors: Aimy Sebastian, Gabriela G Loots
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 80 Pg. 38-47 (03 2018) ISSN: 1532-8600 [Electronic] United States
• PMID: 29080811 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Bone Morphogenetic Proteins
• Genetic Markers
• SOST protein, human

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Bone Morphogenetic Proteins (genetics)
• Disease Models, Animal
• Genetic Markers (genetics)
• Humans
• Hyperostosis (genetics, pathology)
• Osteochondrodysplasias (genetics, pathology)
• Syndactyly (genetics, pathology)