Thyrostimulin regulates osteoblastic bone formation during early skeletal development.
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The ancestral glycoprotein hormone thyrostimulin is a heterodimer of unique GPA2 and GPB5 subunits with high affinity for the thyrotropin receptor (TSHR). Transgenic over-expression of GPB5 in mice results in cranial abnormalities, but the role of thyrostimulin in bone remains unknown. We hypothesized that thyrostimulin exerts paracrine actions in bone and determined; (i) GPA2 and GPB5 expression in osteoblasts and osteoclasts, (ii) the skeletal consequences of thyrostimulin deficiency in GPB5KO mice and (iii) osteoblast and osteoclast responses to thyrostimulin treatment. Gpa2 and Gpb5 expression was identified in the newborn skeleton but declined rapidly thereafter. GPA2 and GPB5 mRNAs were also expressed in primary osteoblasts and osteoclasts at varying concentrations. Juvenile thyrostimulin-deficient mice had increased bone volume and mineralization as a result of increased osteoblastic bone formation. However, thyrostimulin failed to induce a canonical cAMP response or activate the non-canonical Akt, ERK or P38 signaling pathways in primary calvarial or bone marrow stromal cell-derived osteoblasts. Furthermore, thyrostimulin did not directly inhibit osteoblast proliferation, differentiation or mineralization in vitro. These studies identify thyrostimulin as a negative but indirect regulator of osteoblastic bone formation during skeletal development.
Date Issued
2015-05-27
Date Acceptance
2015-05-21
Citation
Endocrinology, 2015, 156 (9), pp.3098-3113
ISSN
1945-7170
Publisher
Endocrine Society
Start Page
3098
End Page
3113
Journal / Book Title
Endocrinology
Volume
156
Issue
9
Copyright Statement
This article has been published under the terms of the Creative Commons Attribution License (CC-BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s)
License URL
Publication Status
Published