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Cited by 35Thyroid Disorders and TreatmentsOsteoarthritis Treatment and MechanismsBone Metabolism and Diseases

Chondrocytes Play a Major Role in the Stimulation of Bone Growth by Thyroid Hormone

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Desjardin, Clémence, Charles, Cyril, Benoist-Lasselin, Catherine, Riviere, Julie, Gilles, Mailys, Chassande, Olivier, Morgenthaler, Caroline, Laloé, Denis +4 more·2014·Endocrinology
DOI 10.1210/en.2014-1109
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Abstract

Thyroid hormone (T3) is required for postnatal skeletal growth. It exerts its effect by binding to nuclear receptors, TRs including TRα1 and TRβ1, which are present in most cell types. These cell types include chondrocytes and osteoblasts, the interactions of which are known to regulate endochondral bone formation. In order to analyze the respective functions of T3 stimulation in chondrocytes and osteoblasts during postnatal growth, we use Cre/loxP recombination to express a dominant-negative TRα1L400R mutant receptor in a cell-specific manner. Phenotype analysis revealed that inhibiting T3 response in chondrocytes is sufficient to reproduce the defects observed in hypothyroid mice, not only for cartilage maturation, but also for ossification and mineralization. TRα1L400R in chondrocytes also results in skull deformation. In the meantime, TRα1L400R expression in mature osteoblasts has no visible effect. Transcriptome analysis identifies a number of changes in gene expression induced by TRα1L400R in cartilage. These changes suggest that T3 normally cross talks with several other signaling pathways to promote chondrocytes proliferation, differentiation, and skeletal growth.

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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 [82]

    In “Comparison with other Thra knock-in mouse models” (page not supplied), the paper reports that patients with THRA mutations share short stature, macrocephaly, and delayed bone age, paralleling skeletal findings in mutant mice. But it also reports marked differences among patients and says different THRA mutations may produce variable phenotypes, so it does not support describing the abnormalities as uniformly consistent. (LLM, conf=0.85)

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Authors
Desjardin, C., Charles, C., Benoist-Lasselin, C., Riviere, J., Gilles, M., Chassande, O., Morgenthaler, C., Laloé, D., Lecardonnel, J., Flamant, F., Legeai-Mallet, L., & Schibler, L.
Affiliations
  • Génétique Animale et Biologie Intégrative (FR)
  • École Normale Supérieure de Lyon (FR)
  • Inserm (FR)
  • Institut National de la Recherche Agronomique (INRA) (C.D., J.R., M.G., C.M., D.L., J.L., L.S.), UMR1313, Biologie Intégrative et Génétique Animale, Jouy-en-Josas, France
  • Université de Bordeaux (FR)
  • Institut Imagine (C.B.-L., L.L.-G.) Institut National de la Santé et de la Recherche Medicale, U1163, Université Paris Descartes, 75015 Paris, France
Corresponding author
Flamant, Frédéric
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2014-08-01
Volume
155
Issue
8
Pages
3123-3135
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2014-1109
OpenAlex
W1997505180
Cited by
35
References
2
Citations by year
2026: 1 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 8 · 2015: 3 · 2014: 1
FWCI
4.56
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Agence Nationale de la Recherche
  • Centre National de la Recherche Scientifique
  • Institut National de la Recherche Agronomique
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
thyroid hormones, chondrocytes, thyroid hormone receptor alpha 1, thyroid hormone receptor beta 1, dominant negative receptor, endochondral ossification, cartilage maturation, bone mineralization, hypothyroidism, skull deformation, chondrocyte proliferation, chondrogenic differentiation, gene expression changes, signaling crosstalk
MeSH terms
Animals, Bone Development, Cell Differentiation, Female, Hypothyroidism, Male, Mice, Inbred C57BL, Mice, Transgenic, Osteoblasts, Osteogenesis, Triiodothyronine, Chondrocytes, Receptor Cross-Talk, Thyroid Hormone Receptors alpha, Mice

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