Bone remodeling is essential for sustaining bone mass, and requires a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Metabolic bone diseases, e.g. osteoporosis, occur when this balance is disrupted. Thyroid hormones play a pivotal role in bone metabolism and are essential for normal skeletal development. The thyroid hormone receptor α (TRα) is expressed in the skeleton and mediates the action of the biological active hormone 3,5,3’-L-triiodothyronine (T3) in bone. A close association between thyroid dysfunction and bone metabolism has been demonstrated. Childhood hypothyroidism causes delayed skeletal development. Patients with hyperthyroidism display strong correlations between low TSH and high bone turnover, reduced bone mineral density, osteoporosis, and increase in fracture risk.
It has been demonstrated that the thyroid stimulating hormone receptor (TSHR) is expressed in bone. TSH, the native ligand of the TSHR, displayed osteoprotective effects independent of thyroid hormones in rodents by preventing bone loss after ovariectomy. Therefore, TSH is suggested to be a fine-tuning regulator of bone homeostasis, which makes the TSHR a plausible therapeutic target. In vitro studies using a human preosteoblast-like cell line stably expressing TSHR, U2OS-TSHR cells, have demonstrated TSHR-induced upregulation of osteoblast marker genes by a combination of G-protein and β-Arrestin-1 mediated signaling pathways. However, TSHR-mediated signaling mechanisms in human bone are only now being delineated.
This Research Topic will include original research articles, reviews, perspectives, and opinion articles providing a comprehensive summary regarding the role of thyroid hormones, the thyroid hormone receptor α, and TSHR-mediated signaling in bone metabolism with emphasis on recent basic and clinical research. The topic is intended to further energize the ongoing discussion of the involvement of thyroid hormones and/or TSH in sustaining bone mass and systemic mineral homeostasis.
Bone remodeling is essential for sustaining bone mass, and requires a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Metabolic bone diseases, e.g. osteoporosis, occur when this balance is disrupted. Thyroid hormones play a pivotal role in bone metabolism and are essential for normal skeletal development. The thyroid hormone receptor α (TRα) is expressed in the skeleton and mediates the action of the biological active hormone 3,5,3’-L-triiodothyronine (T3) in bone. A close association between thyroid dysfunction and bone metabolism has been demonstrated. Childhood hypothyroidism causes delayed skeletal development. Patients with hyperthyroidism display strong correlations between low TSH and high bone turnover, reduced bone mineral density, osteoporosis, and increase in fracture risk.
It has been demonstrated that the thyroid stimulating hormone receptor (TSHR) is expressed in bone. TSH, the native ligand of the TSHR, displayed osteoprotective effects independent of thyroid hormones in rodents by preventing bone loss after ovariectomy. Therefore, TSH is suggested to be a fine-tuning regulator of bone homeostasis, which makes the TSHR a plausible therapeutic target. In vitro studies using a human preosteoblast-like cell line stably expressing TSHR, U2OS-TSHR cells, have demonstrated TSHR-induced upregulation of osteoblast marker genes by a combination of G-protein and β-Arrestin-1 mediated signaling pathways. However, TSHR-mediated signaling mechanisms in human bone are only now being delineated.
This Research Topic will include original research articles, reviews, perspectives, and opinion articles providing a comprehensive summary regarding the role of thyroid hormones, the thyroid hormone receptor α, and TSHR-mediated signaling in bone metabolism with emphasis on recent basic and clinical research. The topic is intended to further energize the ongoing discussion of the involvement of thyroid hormones and/or TSH in sustaining bone mass and systemic mineral homeostasis.