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

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.

A Novel Mutation in THRA Gene Associated With an Atypical Phenotype of Resistance to Thyroid Hormone

“…Impaired ossification, without obvious malformation, is observed in THRA knockout mice (17,18) and mouse models of RTH␣ (19). This has been attributed to a defect in cartilage growth and delayed maturation (20). The malformations observed in this patient were reminiscent of cleidocranial dysplasia (21) resulting from an alteration of the Wnt/Runx2 pathway (22,23).…”

YAP and ERK mediated mechanical strain‐induced cell cycle progression through RhoA and cytoskeletal dynamics in rat growth plate chondrocytes

“…The coordinated recruitment, proliferation, hypertrophy, and apoptosis of growth plate chondrocytes are important to ensure the occurrence of continuous physiological growth . Endochondral ossification is regulated by a variety of endocrine and paracrine hormones, by growth factors and by mechanical loading . It is widely recognized that mechanical loading exerts crucial effects on the development of cartilage and bone tissue at the levels of gene expression, protein translation, and extracellular matrix (ECM) production .…”

Remodeling of the Bone Tissue of Rats of Different Lines After Melatonin Effect

“…BT is extremely sensitive tissue-target for fТ3. It testifies to the important role of thyroid hormones in process of BT growth, development and metabolism [18][19][20][21].…”