Endocrine Regulation on Bone by Thyroid

Abstract

Background: As an endocrine organ, the thyroid acts on the entire body by secreting a series of hormones, and bone is one of the main target organs of the thyroid.

Summary: This review highlights the roles of thyroid hormones and thyroid diseases in bone homeostasis.

Conclusion: Thyroid hormones play significant roles in the growth and development of bone, and imbalance of thyroid hormones can impair bone homeostasis.

Keywords: bone; bone homeostasis; thyroid; thyroid diseases; thyroid hormones.

Figure 1

TH-mediate regulation of chondrocyte proliferation and differentiation. THs promote the differentiation of chondrocyte via Wnt signaling pathway, BMP signaling pathways, and IGF-1 signaling pathway. Furthermore, the expression of Ihh in pre-hypertrophic and hypertrophic chondrocytes induces the expression of PTHrP, which promotes chondrocyte proliferation and inhibits chondrocyte maturation through a negative feedback loop, and the site of hypertrophic chondrocytes determines the length of the bone, therefore, THs regulate the length of long bone by Ihh-PTHrP signaling pathway. Furthermore, BMP can increase the expression of Ihh and abrogates the partial inhibition of the maturation effects of PTHrP to regulate chondrocyte proliferation and maturation, and the increased expression of Runx2 in mature and differentiated chondrocytes is beneficial for stimulating chondrocyte proliferation mediated by Ihh.

Figure 2

Metabolism of THs in bone cells. A brief illustration of the negative feedback regulation of TH mediated by the hypothalamus pituitary-thyroid axis, and DIO2 converts T4 to bioactive T3 in osteoblasts, and DIO3 converts both T3 and T4 to T2 and rT3 in osteoclasts, chondrocytes and osteoblasts.

Figure 3

TH-mediate regulation of osteoblast differentiation. THs promote the differentiation of osteoblasts by activating IGF-1 signaling pathway and BMP signaling pathway, while THs inhibit the differentiation of osteoblasts by inhibiting Wnt/β-catenin signaling pathway. Furthermore, BMP signaling pathway and Wnt signaling pathway interact with each other and promote differentiation of osteoblast by forming a transcriptional complex.

Figure 4

Hyperthyroidism and hypothyroidism on bone. In adult, hyperthyroidism promotes more bone resorption than bone formation, resulting in bone loss, and hypothyroidism impedes bone remodeling, resulting in old bone accumulation, however, bone loss also appears in hypothyroidism after the administration of LT4. In child, hypothyroidism impairs both endochondral and intramembranous ossification, which manifest as delayed closure of fontanelles, persistently patent skull sutures, and short stature, and hyperthyroidism results in craniosynostosis and below-average height.

Figure 5

Immune imbalance in thyroid disease. Normal thyroid cells die due to attacks of B cells and CTL, and gland lobes undergo fibrosis and atrophy, which subsequently leads to hypothyroidism that promotes TSH secretion through negative feedback, then excessive TSH lead to pathological hyperplasia of thyroid folicullar epithelium followed by inducing thyroid cancer. Muchmore, tumor-related macrophages and neutrophils in patients with thyroid cancer can promote invasion and metastases of tumor cells. Furthermore, thyrotropin receptor antibodies (TRAb) produced by B cells stimulate TH production and result in hyperthyroidism.