Role and mechanism of action of Sclerostin in bone

If you need an accessible version of this item, please submit a remediation request.
Date
2017-03
Language
American English
Embargo Lift Date
Committee Members
Degree
Degree Year
Department
Grantor
Journal Title
Journal ISSN
Volume Title
Found At
Elsevier
Abstract

After discovering that lack of Sost/sclerostin expression is the cause of the high bone mass human syndromes Van Buchem disease and sclerosteosis, extensive animal experimentation and clinical studies demonstrated that sclerostin plays a critical role in bone homeostasis and that its deficiency or pharmacological neutralization increases bone formation. Dysregulation of sclerostin expression also underlies the pathophysiology of skeletal disorders characterized by loss of bone mass as well as the damaging effects of some cancers in bone. Thus, sclerostin has quickly become a promising molecular target for the treatment of osteoporosis and other skeletal diseases, and beneficial skeletal outcomes are observed in animal studies and clinical trials using neutralizing antibodies against sclerostin. However, the anabolic effect of blocking sclerostin decreases with time, bone mass accrual is also accompanied by anti-catabolic effects, and there is bone loss over time after therapy discontinuation. Further, the cellular source of sclerostin in the bone/bone marrow microenvironment under physiological and pathological conditions, the pathways that regulate sclerostin expression and the mechanisms by which sclerostin modulates the activity of osteocytes, osteoblasts, and osteoclasts remain unclear. In this review, we highlight the current knowledge on the regulation of Sost/sclerotin expression and its mechanism(s) of action, discuss novel observations regarding its role in signaling pathways activated by hormones and mechanical stimuli in bone, and propose future research needed to understand the full potential of therapeutic interventions that modulate Sost/sclerostin expression.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Delgado-Calle, J., Sato, A. Y., & Bellido, T. (2017). Role and mechanism of action of Sclerostin in bone. Bone, 96, 29–37. https://doi.org/10.1016/j.bone.2016.10.007
ISSN
8756-3282
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
Bone
Source
PMC
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Author's manuscript
Full Text Available at
This item is under embargo {{howLong}}