Role of Thyroid Hormones in Skeletal Development and Bone Maintenance

Abstract

The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art.

Incidence of Thyroid Diseases in Female Saudi Adults Visiting a Tertiary Care Hospital in Riyadh

“…We also measured some of the parameters of bone profile like serum calcium, phosphorus, alkaline phosphatase and vitamin D levels in the participants as it has already been suggested that thyroid hormones play an important role in the homeostasis of calcium and phosphorus levels by their direct action on bone turnover [17,18]. Previous studies carried out on serum calcium and phosphorus levels in thyroid disorders had conflicting results.…”

“…Mineral metabolism (calcium and phosphorus) is frequently disturbed in hyperthyroidism [16]. Thyroid hormones play an important role in the homeostasis of calcium and phosphorus levels by their direct action on bone turnover [17,18]. Previous studies carried out on serum calcium and phosphorus levels in thyroid disorders have had conflicting results.…”

The significance of TRIP11 and T3 signaling pathway in renal cancer progression and survival of patients.

“…Furthermore, patients with achondrogenesis type 1A, a neonatal, lethal form of skeletal dysplasia, bear inactivating mutations in the TRIP11 gene [33]. It is known that thyroid hormones are indispensable for proper development and that mutation in THRs or changes in intracellular T3 levels lead to disturbances in bone formation [38]. These effects are explained mainly by loss of T3-dependent effects on gene expression.…”

Targeting the TSH receptor in thyroid cancer

“…Surface expression of TSHR is estimated at 5000 receptors per cell (Rees Smith et al 1988). TSHR mRNA and protein have been detected in a variety of other human and animal tissues, including neural and immune tissues, ocular muscles and bone (Davies et al 2002, Williams 2011, Bassett & Williams 2016. In particular, the role of TSHR expression in orbital preadipocytes and fibroblasts in the pathogenesis of Graves' ophthalmopathy has been extensively studied (Smith 2015), and there are animal data to support TSHR-mediated bone remodeling (Abe et al 2003, Ma et al 2011.…”