HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0142v1 42/4/269    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bassett, D. Articles by Williams, G. Search for Related Content PubMed PubMed Citation Articles by Bassett, D. Articles by Williams, G.

D Bassett, Metabolic Medicine, Imperial College London, London, W12 0NN, United Kingdom
G Williams, Molecular Endocrinology Group, Imperial College London, London, United Kingdom

Correspondence: Duncan Bassett, Email: d.bassett{at}imperial.ac.uk

Abstract

Analysis of mice harbouring deletions or mutations of thyroid hormone receptor (TR) and β (TRβ) have clarified the complex relationship between central and peripheral thyroid status and emphasised the essential but contrasting roles of thyroid hormone (T3) in skeletal development and adult bone. These studies indicate that TR1 is the predominant TR expressed in bone and that T3 exerts anabolic actions during growth but catabolic actions in the adult skeleton. Examination of key skeletal regulatory pathways in TR mutant mice has identified growth hormone, insulin like growth factor 1 and fibroblast growth factor signalling and the Indian hedgehog/parathyroid hormone-related peptide feed back loop as major targets of T3 action in chondrocytes and osteoblasts. Nevertheless, although increased osteoclastic resorption is a major feature of thyrotoxic bone loss and altered osteoclast activity is central to the skeletal phenotype of TR mutant mice, it remains unclear whether T3 has direct actions in osteoclasts. Detailed future analysis of the molecular mechanisms of T3 action in bone will enhance our understanding of this emerging field and has the potential to identify novel strategies for prevention and treatment of osteoporosis.