A Novel Interaction between Thyroid Hormones and 1,25(OH)2D3 in Osteoclast Formation
Abstract
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).
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Thyroid hormone indirectly promotes osteoclast formation and activation by inducing the expression of cytokines, prostaglandins and the receptor activator of nuclear factor NF-kB ligand.
“Thyroid hormone indirectly promotes osteoclast formation and activation by inducing the expression of cytokines, prostaglandins and the receptor activator of nuclear factor NF-kB ligand [12, 36, 37].”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [37]
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- Authors
- Miura, M., Tanaka, K., Komatsu, Y., Suda, M., Yasoda, A., Sakuma, Y., Ozasa, A., & Nakao, K.
- Affiliations
- Koshien University (JP)
- Corresponding author
- Komatsu, Yasato
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 291
- Issue
- 4
- Pages
- 987-994
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2071207759
- Cited by
- 88
- References
- 0
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 1 · 2018: 3 · 2016: 2 · 2015: 4 · 2014: 2 · 2013: 5 · 2012: 7
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- thyroid hormones, 1,25-dihydroxyvitamin D3, osteoclastogenesis, triiodothyronine, thyroxine, RANKL, primary osteoblasts, secondary osteoporosis, hormone crosstalk, bone resorption
- MeSH terms
- Iodothyronine Deiodinase Type II, Animals, Animals, Newborn, Calcitriol, Carrier Proteins, Cell Line, Cells, Cultured, Dose-Response Relationship, Drug, Drug Synergism, Hematopoietic Stem Cells, Iodide Peroxidase, Kinetics, Membrane Glycoproteins, Osteoblasts, Osteoclasts, RNA, Messenger, Thyroxine, Triiodothyronine, Coculture Techniques, Mice, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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