Genetics of Sost/SOST in sclerosteosis and van Buchem disease animal models
- PMID: 29080811
- DOI: 10.1016/j.metabol.2017.10.005
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.
Keywords: High bone mass; Sclerosteosis; Sclerostin; Sost; van Buchem disease.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Similar articles
-
Sclerostin neutralization unleashes the osteoanabolic effects of Dkk1 inhibition.JCI Insight. 2018 Jun 7;3(11):e98673. doi: 10.1172/jci.insight.98673. eCollection 2018 Jun 7. JCI Insight. 2018. PMID: 29875318 Free PMC article.
-
Novel SOST gene mutation in a sclerosteosis patient from Morocco: a case report.Eur J Med Genet. 2014 Mar;57(4):133-7. doi: 10.1016/j.ejmg.2014.02.007. Epub 2014 Mar 1. Eur J Med Genet. 2014. PMID: 24594238
-
A generalized skeletal hyperostosis in two siblings caused by a novel mutation in the SOST gene.Bone. 2005 Jun;36(6):943-7. doi: 10.1016/j.bone.2005.02.019. Bone. 2005. PMID: 15869924
-
The sclerostin story: from human genetics to the development of novel anabolic treatment for osteoporosis.Hormones (Athens). 2014 Oct-Dec;13(4):323-37. doi: 10.14310/horm.2002.1552. Hormones (Athens). 2014. PMID: 25555179 Review.
-
Sclerostin deficiency in humans.Bone. 2017 Mar;96:51-62. doi: 10.1016/j.bone.2016.10.010. Epub 2016 Oct 11. Bone. 2017. PMID: 27742500 Review.
Cited by
-
Gene Expression and RNA Splicing Imputation Identifies Novel Candidate Genes Associated with Osteoporosis.J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4742-57. doi: 10.1210/clinem/dgaa572. J Clin Endocrinol Metab. 2020. PMID: 32827035 Free PMC article.
-
Advanced Genetic Approaches in Discovery and Characterization of Genes Involved With Osteoporosis in Mouse and Human.Front Genet. 2019 Apr 2;10:288. doi: 10.3389/fgene.2019.00288. eCollection 2019. Front Genet. 2019. PMID: 31001327 Free PMC article. Review.
-
Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease.Bone Res. 2024 Jul 10;12(1):39. doi: 10.1038/s41413-024-00342-8. Bone Res. 2024. PMID: 38987555 Free PMC article. Review.
-
Skeletal endocrinology: where evolutionary advantage meets disease.Bone Res. 2021 May 28;9(1):28. doi: 10.1038/s41413-021-00149-x. Bone Res. 2021. PMID: 34050126 Free PMC article. Review.
-
High Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench.J Bone Miner Res. 2023 Feb;38(2):229-247. doi: 10.1002/jbmr.4715. Epub 2022 Oct 21. J Bone Miner Res. 2023. PMID: 36161343 Free PMC article. Review.
Publication types
MeSH terms
Substances
Supplementary concepts
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
