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Review
. 2013 Jun 28;1(2):146-61.
doi: 10.4248/BR201302004. eCollection 2013 Jun.

Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development

Ha-Young Kim  1 , Subburaman Mohan  2
Affiliations
Review

Role and Mechanisms of Actions of Thyroid Hormone on the Skeletal Development

Ha-Young Kim et al. Bone Res. .

Abstract

The importance of the thyroid hormone axis in the regulation of skeletal growth and maintenance has been well established from clinical studies involving patients with mutations in proteins that regulate synthesis and/or actions of thyroid hormone. Data from genetic mouse models involving disruption and overexpression of components of the thyroid hormone axis also provide direct support for a key role for thyroid hormone in the regulation of bone metabolism. Thyroid hormone regulates proliferation and/or differentiated actions of multiple cell types in bone including chondrocytes, osteoblasts and osteoclasts. Thyroid hormone effects on the target cells are mediated via ligand-inducible nuclear receptors/transcription factors, thyroid hormone receptor (TR) α and β, of which TRα seems to be critically important in regulating bone cell functions. In terms of mechanisms for thyroid hormone action, studies suggest that thyroid hormone regulates a number of key growth factor signaling pathways including insulin-like growth factor-I, parathyroid hormone related protein, fibroblast growth factor, Indian hedgehog and Wnt to influence skeletal growth. In this review we describe findings from various genetic mouse models and clinical mutations of thyroid hormone signaling related mutations in humans that pertain to the role and mechanism of action of thyroid hormone in the regulation of skeletal growth and maintenance.

Keywords: bone; bone cells; cartilage; growth factors; thyroid hormone.

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Figures

Figure 1
Figure 1
TRH-TSH-T3 feedback loop. The hypothalamic neurons secrete thyrotropin releasing hormone (TRH) which is carried down to the adenohypophysis of the pituitary by the hypothalamic portal vein where it releases thyroid stimulating hormone (TSH). The released TSH reaches thyroid glands via blood stream to bind to TSH receptor (TSHR) to stimulate production and release of thyroxin (T4) and T3. T3 exerts its actions on bone mainly by binding to TRa. TSH can also act directly on bone cells by binding to TSHR. Increased levels of T3 can act by negative feedback loop via TRβ to inhibit release of TRH and TSH, thereby preventing hyperparathyroidism.
Figure 2
Figure 2
Mechanisms for T3 regulation of chondrocyte differentiation. T3 can modulate local actions of growth factors such as IGF-I, FGFs, Wnts, Ihh and PTHrp to regulate proliferation and differentiation of cells of chondrocytic lineage. The differentiating promoting actions of T3 on chondrocytes are known to be mediated via inhibition of Sox9 and stimulation of Runx2 expression.
Figure 3
Figure 3
Mechanisms for T3 regulation of osteoblast differentiation. T3 increases local IGF-I actions by modulating production of IGF-I and/or its binding proteins and thereby stimulate differentiation of mesenchymal cells into osteoblast lineage. T3 can also stimulate local FGF actions by increasing FGF receptor expression in osteoblasts. T3 can also exert direct effects via TRE to regulate transcription of bone formation genes.
Figure 4
Figure 4
Model of TH regulation of skeletal growth in mice. It is proposed that the increase in IGF-I expression and bone accretion during prepubertal and pubertal growth periods are mediated via TH and GH-dependent mechanisms, respectively. Some of the effects of TH on bone growth are direct and occur independent of GH.
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References

    1. Harvey CB, O'Shea PJ, Scott AJ, Robson H, Siebler T, Shalet SM, Samarut J, Chassande O, Williams GR. Molecular mechanisms of thyroid hormone effects on bone growth and function. Mol Genet Metab. 2002;75:17–30. - PubMed
    1. Rivkees SA, Bode HH, Crawford JD. Long-term growth in juvenile acquired hypothyroidism: the failure to achieve normal adult stature. N Engl J Med. 1988;318:599–602. - PubMed
    1. Segni M, Leonardi E, Mazzoncini B, Pucarelli I, Pasquino AM. Special features of Graves' disease in early childhood. Thyroid. 1999;9:871–877. - PubMed
    1. Abel ED, Ahima RS, Boers ME, Elmquist JK, Wondisford FE. Critical role for thyroid hormone receptor beta2 in the regulation of paraventricular thyrotropin-releasing hormone neurons. J Clin Invest. 2001;107:1017–1023. - PMC - PubMed
    1. Forrest D, Hanebuth E, Smeyne RJ, Everds N, Stewart CL, Wehner JM, Curran T. Recessive resistance to thyroid hormone in mice lacking thyroid hormone receptor beta: evidence for tissue-specific modulation of receptor function. EMBO J. 1996;15:3006–3015. - PMC - PubMed