Thyroid hormone actions in cartilage and bone.

Thyroid hormones exert widespread and complex actions in almost all tissues during development, throughout childhood and in adults. The skeleton is an important T3-target tissue that exemplifies these processes, and yet understanding of the specific cellular and molecular mechanisms of T3 action in bone and cartilage remains incomplete. Here, the skeleton is considered as a T3-target tissue. The actions of thyroid hormones during skeletal development and in chondrocytes and growth plate cartilage during post-natal linear growth are outlined. The physiological importance of these actions are discussed in relation to patients with autosomal dominant mutations in genes encoding the thyroid hormone receptors TRα1 and TRβ, and in mice harbouring deletions or mutations of the orthologous genes. The role of thyroid hormones and the control of T3 action in bone turnover and maintenance are also outlined, and T3 action in bone-forming osteoblasts and bone-resorbing osteoclasts discussed. The physiological and functional consequences of T3 action in bone are considered in relation to mutant mouse models and to effects on bone mineral density and fracture susceptibility in humans. Finally, new studies identifying a putative role for thyroid hormone metabolism in articular cartilage maintenance and the pathogenesis of osteoarthritis are considered. The pharmacological context of these new findings is discussed, emphasising the importance of this emerging field of study in thyroid hormone pathophysiology.