The molecular actions of thyroid hormone in bone

Thyroid hormone (T3) is essential for the normal development of endochondral and intramembranous bone and plays an important role in the linear growth and maintenance of bone mass. Childhood T3 deficiency results in retardation of skeletal development and growth arrest, whereas T3 excess leads to accelerated growth and bone formation. In adult thyrotoxicosis, there is increased bone remodelling, characterized by an imbalance between bone resorption and formation, which results in net bone loss and an increased risk for posteoporotic fracture. These clinical observations demonstrate the importance of T3 in skeletal development and metabolism. Nevertheless, the molecular mechanisms of T3 action in bone are poorly understood. Here, we provide an overview of T3 regulation of chondrocytes, osteoblasts and osteoclasts, and the actions of thyroid hormone receptor (TR) isoforms in skeletal development. The possible roles of T3 and TRs in nuclear receptor crosstalk, prereceptor ligand metabolism, heparan sulfate proteoglycan synthesis and angiogenesis are also considered.