A novel interaction between thyroid hormones and 1,25(OH)(2)D(3) in osteoclast formation.
Thyroid hormones enhance osteoclast formation and their excess is an important cause of secondary osteoporosis. 3,5,3' -Triiodo-L-thyronine (T3) induced the mRNA expression of receptor activator of nuclear factor-kappa B ligand (RANKL), which is a key molecule in osteoclast formation, in primary osteoblastic cells (POB). This effect was amplified in the copresence of 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Although T3 alone did not induce octeoclasts in coculture of bone marrow cells with POB, T3 enhanced 1,25(OH)(2)D(3)-induced osteoclast formation. Thyroxine (T4) also enhanced 1,25(OH)(2)D(3)-induced osteoclast formation. These data suggested that T4 was locally metabolized to T3 for its action, since T4 is a prohormone with little hormonal activity. The mRNA expression of type-2 iodothyronine deiodinase (D2), which is responsible for maintaining local T3 concentration, was induced by 1,25(OH)(2)D(3) dose- and time-dependently. Our data would facilitate our understanding of the mechanism of osteoclast formation by thyroid hormones and suggest a novel interaction between thyroid hormones and 1,25(OH)(2)D(3).
Miura
Masako
M
Department of Medicine and Clinical Science, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan.
Tanaka
Kiyoshi
K
Komatsu
Yasato
Y
Suda
Michio
M
Yasoda
Akihiro
A
Sakuma
Yoko
Y
Ozasa
Ami
A
Nakao
Kazuwa
K
D000818:Animals; D000831:Animals, Newborn; D002117:Calcitriol / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D007453:Iodide Peroxidase / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000502:physiology*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000096:biosynthesis; D053246:Receptor Activator of Nuclear Factor-kappa B; D013974:Thyroxine / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*; D000097564:Iodothyronine Deiodinase Type II
D002117:Calcitriol; D002352:Carrier Proteins; D007453:Iodide Peroxidase; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse