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

Endocrinology. 2014 Aug;155(8):3123-35. doi: 10.1210/en.2014-1109. Epub 2014 Jun 10.

Abstract

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 TRα1(L400R) 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. TRα1(L400R) in chondrocytes also results in skull deformation. In the meantime, TRα1(L400R) expression in mature osteoblasts has no visible effect. Transcriptome analysis identifies a number of changes in gene expression induced by TRα1(L400R) in cartilage. These changes suggest that T3 normally cross talks with several other signaling pathways to promote chondrocytes proliferation, differentiation, and skeletal growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Development*
  • Cell Differentiation
  • Chondrocytes / cytology
  • Chondrocytes / physiology*
  • Female
  • Hypothyroidism / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Osteoblasts / physiology*
  • Osteogenesis
  • Receptor Cross-Talk
  • Thyroid Hormone Receptors alpha / physiology*
  • Triiodothyronine / physiology

Substances

  • Thyroid Hormone Receptors alpha
  • Triiodothyronine