A Study on the metabolism and action of thyroid hormones in the bone and cartilage.

甲状腺激素在骨和软骨中的代谢和作用的研究。

• 批准号: 13671166
• 负责人: TANAKA Kiyoshi
• 金额: $ 1.92万
• 依托单位: Koshien University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671166/
• 关键词: thyroid hormone; deiodinase; growth plate; osteoblast; osteoclast; vitamin D; ビタミンD3; クレチン症; ATDC5細胞

Thyroid hormone deficiency is one of the important causes of dwarfism. The underlying mechanism, however, remains to be elucidated. We then studied the thyroid hormone effect on growth plate cartilage with emphasis on the metabolism. Thyroxin (T4) must be converted to 3,5,3,-triiodothyronine (T3) catalyzed by 5'-deiodinase for its action. We have found that 5'-deiodinase is present in ATDC-5 cell that is a good model to study the cartilage development. Both T4 and T3 enhanced the differentiation markers of cartilage. When thyroid hormones were added to the organ culture system, they markedly stimulated the longitudinal bone growth. Iopanoic acid, an inhibitor of 5'-deiodinase, abolished T4 action without affecting T3 action.We also studied the bone effects of thyroid hormones on the bone, since thyroid hormone excess is known to be an important cause of secondary osteoporosis with increased bone resorption. 5'-deiodinase was present in primary-cultured osteoblast. Thyroid hormones enhanced the expression of RANKL that is a key molecule in osteoclast formation. Although thyroid hormones alone did not induce osteoclast formation, they markedly enhanced the vitamin D-induced osteoclast formation. Thus a novel interaction between thyroid hormones and vitamin D in osteoclast formation was suggested.In this study, we have shown the importance of local activation of thyroid hormones for their skeletal effects.

甲状腺激素缺乏是侏儒症的重要原因之一。然而，其潜在的机制仍有待阐明。然后，我们研究了甲状腺激素对生长板软骨的影响，重点是代谢。甲状腺激素(T4)必须在5‘-脱碘酶的催化下转化为3，5，3-三碘甲状腺原氨酸(T3)才能发挥作用。我们发现ATDC-5细胞中存在5‘-脱碘酶，是研究软骨发育的良好模型。T4和T3均增强软骨分化标志物。在器官培养体系中加入甲状腺激素，可明显促进骨的纵向生长。我们还研究了甲状腺激素对骨骼的影响，因为甲状腺激素过量是继发性骨质疏松症的重要原因，骨吸收增加。5‘-脱碘酶存在于原代培养的成骨细胞中。甲状腺激素促进RANKL的表达，RANKL是破骨细胞形成的关键分子。虽然单独的甲状腺激素不能诱导破骨细胞的形成，但它们显著促进了维生素D诱导的破骨细胞的形成。因此，甲状腺激素和维生素D在破骨细胞形成中的一种新的相互作用被提出。在这项研究中，我们已经证明了甲状腺激素的局部激活对于它们的骨骼效应的重要性。

项目成果

Miura A., Tanaka K et al.: "Thyroid Hormones Promote Chondrocyte Differentiation in Mouse ATDC5 Cells and Stimulate Endochondral Ossification in Fetal Mouse Tibiae through lodothyronine Deiodinases in the Growth Plate"J Bone Miner Res. (印刷中). (2002)

Miura A.、Tanaka K 等人：“甲状腺激素通过生长板中的碘甲腺原氨酸脱碘酶促进小鼠 ATDC5 细胞中的软骨细胞分化并刺激胎儿小鼠胫骨中的软骨内骨化”J Bone Miner Res（2002 年出版）。

Thyroid hormones promote chondrocyte differentiation in mouse ATDC 5 cells and stimulate endochondral ossification in fetal muse tibias through iodothyronine deiodinause in the growth plate.

甲状腺激素促进小鼠 ATDC 5 细胞的软骨细胞分化，并通过生长板中的碘甲状腺原氨酸脱碘刺激胎儿小鼠胫骨的软骨内骨化。

• 发表时间: 2002
• 期刊: Journal of Bone and Mineral Research 17
• 作者: Miura M

三浦晶子, 田中清 (他): "A novel interaction between thyroid hormones and 1,25(OH)_2D_3 in Osteoclast formation"Biochem Biophys Res Commun. 291. 987-994 (2002)

Akiko Miura、Kiyoshi Tanaka (等人)：“破骨细胞形成中甲状腺激素和 1,25(OH)_2D_3 之间的新型相互作用”Biochem Biophys Res Commun. 291. 987-994 (2002)

A novel interaction between thyroid hormones and 1,25(OH)2D3 in osteoclast formation.

甲状腺激素和 1,25(OH)2D3 在破骨细胞形成中的新型相互作用。

• 发表时间: 2002
• 期刊: Biochemical and Biophysical Research Communication 291
• 作者: Miura M

Thyroid hormones promote chondrocyte differentiation in mouse ATDC5 cells and stimulate endochondral ossification in fetal mouse tibias through iodothyronine deiodinases in the growth plate.

甲状腺激素促进小鼠 ATDC5 细胞的软骨细胞分化，并通过生长板中的碘甲状腺原氨酸脱碘酶刺激胎儿小鼠胫骨的软骨内骨化。

• 发表时间: 2002
• 期刊: Journal of Bone and Mineral Research 17
• 作者: Miura M;Tanaka K et al.
• 通讯作者: Tanaka K et al.