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

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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.