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Cited by 8Thyroid Disorders and TreatmentsBone Metabolism and DiseasesGrowth Hormone and Insulin-like Growth Factors

Role of Thyroid Hormone Receptor-α1 in Endochondral Ossification

Williams, Graham R.·2014·Endocrinology
DOI 10.1210/en.2014-1527
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Abstract

Thyroid hormones are important regulators of postnatal skeletal development, linear growth, and bone maintenance. Thyroid hormone deficiency during childhood results in growth retardation and delayed bone age and tooth eruption, with epiphyseal dysgenesis and linear growth arrest evident in severe cases (1). Treatment of hypothyroid children with T4 results in rapid catch-up of bone age and growth, although short stature may persist in individuals who have prolonged hormone deficiency prior to treatment (2, 3). In contrast, thyrotoxicosis induces premature bone maturation and increases linear growth velocity, although the early closure of the growth plates and premature fusion of the sutures of the skull can lead to persistent short stature and craniosynostosis in children with severe or undiagnosed and continuing hyperthyroidism (4). Overall, these observations reveal exquisite sensitivity of the postnatal skeleton to thyroid hormones and the requirement for euthyroid status to ensure normal bone development and growth. Endochondral ossification is the mechanism underlying bone formation on a cartilage scaffold and the process by which linear growth proceeds in the epiphyseal growth plates (5). Mesenchyme progenitor cells condense and differentiate into chondrocytes, which proliferate and secrete matrix proteins to form a cartilage template for bone formation. At the primary ossification center a tightly regulated program of chondrocyte organization, proliferation, hypertrophic differentiation, and apoptosis results in cartilage mineralization. Vascular invasion and migration of osteoblasts leads to the replacement of mineralized cartilage with trabecular bone. In addition, mesenchyme progenitors condense within perichondrial regions surrounding cartilage and differentiate into osteoblasts, which, via intramembranous ossification, directly form a collar of cortical bone (5). Subsequently, secondary ossification centers form at the ends of long bones, but they remain separated from the primary ossification center by the epiphyseal growth plates. An organized program of chondrocyte proliferation, hypertrophy, and apoptosis continues in the growth plates. Endochondral ossification thus mediates longitudinal growth until adulthood when the epiphyses fuse and linear growth ceases (5).

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  • Together, the reports define a new genetic disorder, RTHα, characterized by profound and consistent developmental abnormalities of the skeleton that recapitulate findings in mice with dominant-negative Thra mutations.

    “Together, these reports define a new genetic disorder, RTHα, characterized by profound and consistent developmental abnormalities of the skeleton that recapitulate findings in mice with dominant-negative Thra mutations [80–85].”

    From Thyroid diseases and bone health (2018) · cites this paper as [85]

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Authors
Williams, G. R.
Affiliations
Imperial College London (GB)
Corresponding author
Williams, Graham R.
ORCID
Williams, Graham R.
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2014-08-01
Volume
155
Issue
8
Pages
2747-2750
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2014-1527
OpenAlex
W2031953721
Cited by
8
References
26
Citations by year
2025: 2 · 2021: 1 · 2018: 1 · 2017: 1 · 2016: 3
FWCI
1.07
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Imperial College London
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
thyroid hormone receptor alpha 1, endochondral ossification, thyroid hormones, skeletal development, linear growth, chondrocyte hypertrophy, chondrocyte apoptosis, growth plate, growth retardation, thyrotoxicosis, craniosynostosis, short stature
MeSH terms
Animals, Bone Development, Female, Male, Osteoblasts, Chondrocytes, Thyroid Hormone Receptors alpha

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