A Novel Interaction between Thyroid Hormones and 1,25(OH)2D3 in Osteoclast Formation

Miura, Masako; Tanaka, Kiyoshi; Komatsu, Yasato; Suda, Michio; Yasoda, Akihiro; Sakuma, Yoshiharu; Ozasa, Ami; Nakao, Kazuwa

doi:10.1006/bbrc.2002.6561

Cited by 80 publications

(58 citation statements)

References 33 publications

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“…Earlier reports showed that T3 stimulated osteoclastic bone resorption in the presence of osteoblasts, but not in their absence (95)(96). These findings imply that TH indirectly stimulates osteoclasts via increased expression of RANKL and other cytokines involved in osteoclastogenesis including interleukin 6 (IL-6), IL-8 and prostaglandin E2 (PGE2) in osteoblasts (92,(97)(98). Several studies have demonstrated apparent expression of TR proteins in all bone cell lineages, however, it is not clear whether osteoclasts express TRα1 and TRβ1 mRNAs because currently available TR antibodies are of low affinity, thus compromising the detection of endogenous TRs (75,99).…”

Section: Effects Of T3 In Bone Cells In Vitro Chondrocytesmentioning

confidence: 96%

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

Kim

Mohan

2013

Bone Res.

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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: thyroid hormone; bone; cartilage; growth factors; bone cells Bone Research (2013) 2: 146-161. doi: 10.4248/BR201302004 IntroductionThyroid hormone (TH) plays an important role in normal endochondral ossification and is essential for skeletal development, linear growth, maintenance of bone mass, and efficient fracture healing ( 1). Juvenile hypothyroidism causes growth arrest with delayed bone formation and mineralization, and T4 replacement induces rapid catch-up growth (2). By contrast, childhood thyrotoxicosis accelerates bone formation with premature closure of the growth plates and skull sutures, leading to short stature and craniosynostosis (3). Although there is considerable evidence regarding the importance of TH in skeletal development, the molecular mechanisms of TH action in bone are poorly understood. In this chapter, we discuss regulation and mechanisms of action of TH during skeletal development with particular emphasis on areas in which recent advances have been made. Physiology of TH: Regulation, metabolism and TH receptorRegulation Systemic TH levels are maintained by the classical negative feedback loop involving the hypothalamus-pituitary--thyroid (HPT) axis ( Figure 1). Thyrotropin releasing hormone (TRH) is synthesized in the paraventricular nucleus (PVN) of the hypothalamus and stimulates synthesis and secretion of thyroid stimulating hormone (TSH) fromHa-Young Kim et al. www.boneresearch.org | Bone Research 147thyrotroph cells in the anterior pituitary gland. TSH subsequently acts via the TSH receptor (TSHR) on thyroid follicular cells to stimulate synthesis and release of 3,5...

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Section: Effects Of T3 In Bone Cells In Vitro Chondrocytesmentioning

confidence: 96%

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

Kim

Mohan

2013

Bone Res.

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“…The pathophysiology of osteoporosis in hyperthyroidism is multifactorial (4,5), including shortening of the bone remodeling cycle (6) and acceleration of bone turnover (7). Thyroid hormone indirectly promotes osteoclast formation and activation by inducing the expression of cytokines, prostaglandins, and the receptor activator of nuclear factor NFkB ligand (RANKL) (8)(9)(10). Apart from overt hyperthyroidism, subclinical hyperthyroidism also appears to be associated with decreased bone mineral density (BMD) as reviewed by Heemstra et al (3,11,12).…”

Section: Introductionmentioning

confidence: 99%

Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma.

Heemstra

Deure

Peeters

et al. 2008

European Journal of Endocrinology

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Objective: It has been proposed that TSH has thyroid hormone-independent effects on bone mineral density (BMD) and bone metabolism. This concept is still controversial and has not been studied in human subjects in detail. We addressed this question by studying relationships between serum TSH concentration and indicators of bone turnover, after controlling for triiodothyronine (T 3 ), free thyroxine (FT 4 ), and non-thyroid factors relevant to BMD and bone metabolism. We also studied the contribution of the TSH receptor (TSHR)-Asp727Glu polymorphism to these relationships. Design: We performed a cross-sectional study with 148 patients, who had been thyroidectomized for differentiated thyroid carcinoma. Methods: We measured BMD of the femoral neck and lumbar spine. FT 4 , T 3 , TSH, bone-specific alkaline phosphatase, procollagen type 1 aminoterminal propeptide levels, C-cross-linking terminal telopeptide of type I collagen, and urinary N-telopeptide of collagen cross-links were measured. Genotypes of the TSHR-Asp727Glu polymorphism were determined by Taqman assay. Results: We found a significant, inverse correlation between serum TSH levels and indicators of bone turnover, which was independent of serum FT 4 and T 3 levels as well as other parameters influencing bone metabolism. We found that carriers of the TSHR-Asp727Glu polymorphism had an 8.1% higher femoral neck BMD, which was, however, no longer significant after adjusting for body mass index. Conclusion: We conclude that in this group of patients, serum TSH was related to indicators of bone remodeling independently of thyroid hormone levels. This may point to a functional role of the TSHR in bone in humans. Further research into this mechanism needs to be performed. European Journal of Endocrinology 159 69-76

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“…TCE reduced osteoclast differentiation in the differentiation stage with M-CSF and TGF-␤. Osteoclasts are specialized cells derived from the macrophage hematopoietic lineage, and they undergo differentiation in co-cultures of bone marrow and stromal cells (20,21). TCE suppressed the early stage of differentiation, in which bone marrow cells are stimulated by M-CSF.…”

Section: Discussionmentioning

confidence: 99%

Suppressive Effects of the Leaf of Terminalia catappa L. on Osteoclast Differentiation In Vitro and Bone Weight Loss In Vivo

Koyama

Nakajima

Nishimoto

et al. 2012

J Nutr Sci Vitaminol

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Summary Oral administration of Terminalia catappa extract (TCE; 1,000 mg/kg) for 5 wk suppressed bone weight loss and trabecular bone loss in ovariectomized mice. An in vitro experiment showed that TCE (1.3-20 g/mL) did not increase alkaline phosphatase activity, which would indicate osteoclast formation, in osteoblast-like 3T3-L1 cells. On the other hand, TCE (12.5 g/mL) markedly decreased the number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells, which would indicate osteoclast formation, in a co-culture system (bone marrow cells/osteoblastic UAMS-32 cells). A detailed analysis of the stages of osteoclast differentiation revealed that TCE mainly suppressed the differentiation of bone marrow mononuclear cells into osteoclast progenitor cells in the presence of M-CSF and TGF-␤ . An additional experiment using fractionated TCE revealed that the watersoluble fraction suppressed the bone weight loss in OVX-mice and osteoclast differentiation in vitro. Therefore, the suppressive effects of TCE on bone weight loss in mice might be due to the suppressive effects of highly polar components on the early stage of osteoclast differentiation.

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A Novel Interaction between Thyroid Hormones and 1,25(OH)2D3 in Osteoclast Formation

Cited by 80 publications

References 33 publications

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

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

Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma.

Suppressive Effects of the Leaf of Terminalia catappa L. on Osteoclast Differentiation In Vitro and Bone Weight Loss In Vivo

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