Chondrocytes Play a Major Role in the Stimulation of Bone Growth by Thyroid Hormone

Thyroid hormone (T3) is required for postnatal skeletal growth. It exerts its effect by binding to nuclear receptors, TRs including TRα1 and TRβ1, which are present in most cell types. These cell types include chondrocytes and osteoblasts, the interactions of which are known to regulate endochondral...

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Published inEndocrinology (Philadelphia) Vol. 155; no. 8; pp. 3123 - 3135
Main Authors Desjardin, Clémence, Charles, Cyril, Benoist-Lasselin, Catherine, Riviere, Julie, Gilles, Mailys, Chassande, Olivier, Morgenthaler, Caroline, Laloé, Denis, Lecardonnel, Jérôme, Flamant, Frédéric, Legeai-Mallet, Laurence, Schibler, Laurent
Format Journal Article
LanguageEnglish
Published United States Endocrine Society 01.08.2014
Oxford University Press
Subjects
Animals
Bone Development
Cell Differentiation
Chondrocytes - cytology
Chondrocytes - physiology
Female
Hypothyroidism - physiopathology
Life Sciences
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Osteoblasts - physiology
Osteogenesis
Receptor Cross-Talk
Thyroid Hormone Receptors alpha - physiology
Triiodothyronine - physiology
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Summary:Thyroid hormone (T3) is required for postnatal skeletal growth. It exerts its effect by binding to nuclear receptors, TRs including TRα1 and TRβ1, which are present in most cell types. These cell types include chondrocytes and osteoblasts, the interactions of which are known to regulate endochondral bone formation. In order to analyze the respective functions of T3 stimulation in chondrocytes and osteoblasts during postnatal growth, we use Cre/loxP recombination to express a dominant-negative TRα1L400R mutant receptor in a cell-specific manner. Phenotype analysis revealed that inhibiting T3 response in chondrocytes is sufficient to reproduce the defects observed in hypothyroid mice, not only for cartilage maturation, but also for ossification and mineralization. TRα1L400R in chondrocytes also results in skull deformation. In the meantime, TRα1L400R expression in mature osteoblasts has no visible effect. Transcriptome analysis identifies a number of changes in gene expression induced by TRα1L400R in cartilage. These changes suggest that T3 normally cross talks with several other signaling pathways to promote chondrocytes proliferation, differentiation, and skeletal growth.
Bibliography:This study was funded, in part, by a starting grant from INRA Animal genetics Department and UMR1313 GABI and EuroGrow (FP6-LSHM-CT-2007-037471). This work was supported by the Thyrogenomic2 ANR grant (to F.F.).
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ISSN:0013-7227
1945-7170
DOI:10.1210/en.2014-1109