Mechanisms of action of thyroid hormones in the skeleton

Wójcicka, Anna; Bassett, J. H. Duncan; Williams, Graham R.

doi:10.1016/j.bbagen.2012.05.005

Cited by 91 publications

(100 citation statements)

References 82 publications

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“…It should be noted that thyroid hormone can also act directly on target tissues such as growth plate chondrocytes, independent of liver-derived IGF-1. Reduced bone growth, and possibly other phenotypes observed in our mutant mice, might therefore be caused by a combination of reduced circulating IGF-1 and reduced thyroid hormone receptor activation in the target tissue (65,66).…”

Section: Figurementioning

confidence: 99%

Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span

Watson¹,

Solomon²,

Li³

et al. 2013

J. Clin. Invest.

110

140

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Human ATRX mutations are associated with cognitive deficits, developmental abnormalities, and cancer. We show that the Atrx-null embryonic mouse brain accumulates replicative damage at telomeres and pericentromeric heterochromatin, which is exacerbated by loss of p53 and linked to ATM activation. ATRX-deficient neuroprogenitors exhibited higher incidence of telomere fusions and increased sensitivity to replication stressinducing drugs. Treatment of Atrx-null neuroprogenitors with the G-quadruplex (G4) ligand telomestatin increased DNA damage, indicating that ATRX likely aids in the replication of telomeric G4-DNA structures. Unexpectedly, mutant mice displayed reduced growth, shortened life span, lordokyphosis, cataracts, heart enlargement, and hypoglycemia, as well as reduction of mineral bone density, trabecular bone content, and subcutaneous fat. We show that a subset of these defects can be attributed to loss of ATRX in the embryonic anterior pituitary that resulted in low circulating levels of thyroxine and IGF-1. Our findings suggest that loss of ATRX increases DNA damage locally in the forebrain and anterior pituitary and causes tissue attrition and other systemic defects similar to those seen in aging.

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Section: Figurementioning

confidence: 99%

Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span

Watson¹,

Solomon²,

Li³

et al. 2013

J. Clin. Invest.

110

140

View full text Add to dashboard Cite

show abstract

“…Overt hyperthyroidism is associated with an increased risk of osteoporosis, while whether subclinical hyperthyroidism affects the skeleton is under debate [7,8]. Effects of the latter on bone mineral density (BMD) have been addressed in a number of studies with somewhat controversial results [9][10][11][12][13][14][15]. The current understanding is that subclinical hyperthyroidism is a risk factor for osteoporosis in postmenopausal women but not in premenopausal women or male patients [10].…”

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confidence: 99%

Bone mineral density in treated at a young age for differentiated thyroid cancer after Chernobyl female patients on TSH-suppressive therapy receiving or not Calcium-D3 supplementation

et al. 2015

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“…Dysregulation in the production and/or actions of any of the factors that regulate endochondral ossification can result in skeletal diseases including chondrodysplasias and osteoarthritis (21, 40). Although the processes leading to POC formation have been well established, signaling pathways that stimulate SOC formation are not well understood.Thyroid hormone (TH) is known to play an important role in normal endochondral ossification and is essential for skeletal development, linear growth, maintenance of bone density, and efficient fracture healing (20,45,47,48). Juvenile hypothyroidism causes dwarfism with delayed bone formation and mineralization, while TH replacement induces rapid catch-up growth (1,20,44,45).…”

mentioning

confidence: 99%

“…Thyroid hormone (TH) is known to play an important role in normal endochondral ossification and is essential for skeletal development, linear growth, maintenance of bone density, and efficient fracture healing (20,45,47,48). Juvenile hypothyroidism causes dwarfism with delayed bone formation and mineralization, while TH replacement induces rapid catch-up growth (1,20,44,45).…”

mentioning

confidence: 99%

Thyroid hormone receptor-β1 signaling is critically involved in regulating secondary ossification via promoting transcription of the Ihh gene in the epiphysis

Xing

Aghajanian

Goodluck

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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roid hormone (TH) action is mediated through two nuclear TH receptors, THR␣ and THR␤. Although the role of THR␣ is well established in bone, less is known about the relevance of THR␤-mediated signaling in bone development. On ther basis of our recent finding that TH signaling is essential for initiation and formation of secondary ossification center, we evaluated the role of THRs in mediating TH effects on epiphysial bone formation. Two-day treatment of TH-deficient Tshr Ϫ/Ϫ mice with TH increased THR␤1 mRNA level 3.4-fold at day 7 but had no effect on THR␣1 mRNA level at the proximal tibia epiphysis. Treatment of serum-free cultures of tibias from 3-day-old mice with T3 increased THR␤1 expression 2.1-and 13-fold, respectively, at 24 and 72 h. Ten-day treatment of Tshr Ϫ/Ϫ newborns (days 5-14) with THR␤1 agonist GC1 at 0.2 or 2.0 g/day increased BV/TV at day 21 by 225 and 263%, respectively, compared with vehicle treatment. Two-day treatment with GC1 (0.2 g/day) increased expression levels of Indian hedgehog (Ihh) 100-fold, osterix 15-fold, and osteocalcin 59-fold compared with vehicle at day 7 in the proximal tibia epiphysis. Gel mobility shift assay demonstrated that a putative TH response element in the distal promoter of mouse Ihh gene interacted with THR␤1. GC1 treatment (1 nM) increased Ihh distal promoter activity 20-fold after 48 h in chondroctyes. Our data suggest a novel role for THR␤1 in secondary ossification at the epiphysis that involves transcriptional upregulation of Ihh gene. thyroid hormones; ossification; bone formation; osteoblasts; chondrocytes; hypothyroidism; Indian hedge hog ENDOCHONDRAL OSSIFICATION is one of two essential processes required for fetal development of the mammalian skeletal system and for fracture healing. Unlike intramembranous ossification, which is the other process by which mesenchymal cells from the cranial neural crest, sclerotomes, and lateral plate mesoderm migrate and proliferate, forming mesenchymal condensations, cartilage is present and replaced by trabecular bone during endochondral ossification (16,35). There are two centers of ossification for endochondral ossification, a primary and a secondary center. The primary ossification center (POC) usually appears in the diaphysis of the long bones or in the body of the irregular bones during prenatal development while the secondary ossification center (SOC) occurs in the epiphysis of long bones at the time of birth in mammals (11). Endochondral ossification at the POC is tightly regulated by a number of growth factors (PTHrp, IHH, IGF-I, BMP/TGF␤, Wnt, VEGF) and transcription factors (Sox9, Runx2, osterix, ␤-catenin) (3, 10, 21-23, 29, 42, 53). Dysregulation in the production and/or actions of any of the factors that regulate endochondral ossification can result in skeletal diseases including chondrodysplasias and osteoarthritis (21, 40). Although the processes leading to POC formation have been well established, signaling pathways that stimulate SOC formation are not well understood.Thyroid hormone (TH) is known ...

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Mechanisms of action of thyroid hormones in the skeleton

Cited by 91 publications

References 82 publications

Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span

Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span

Bone mineral density in treated at a young age for differentiated thyroid cancer after Chernobyl female patients on TSH-suppressive therapy receiving or not Calcium-D3 supplementation

Thyroid hormone receptor-β1 signaling is critically involved in regulating secondary ossification via promoting transcription of the Ihh gene in the epiphysis

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