ArticleThyroid : official journal of the American Thyroid Association2011
The influence of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies on osteoclastogenesis.
Article in Thyroid : official journal of the American Thyroid Association, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Association between serum TSH concentration and bone mineral density: an umbrella review.Hormones (Athens, Greece) · 2024Pooled it
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study of Jianyao Migu Granules in the Treatment of Osteopenic Low Back Pain.Journal of pain research · 2022Trial
- Neuroendocrine and neural control of bone mass in health and disease.The Journal of clinical investigation · 2026Review
- The influence of hormonal changes during pregnancy on bone metabolism - a mini review.Frontiers in endocrinology · 2026Review
- G-protein coupled receptors synergy in bone health: new avenues for osteoporosis detection andFrontiers in endocrinology · 2025Review
- Neuroendocrinology of bone.Pituitary · 2024Review
- TSH-secreting pituitary adenomas and bone.Pituitary · 2024Article
- Risk factors of primary SjögrenZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Review
- Mechanisms of thyrotropin receptor-mediated phenotype variability deciphered by gene mutations and M453T-knockin model.JCI insight · 2024Article
- Pituitary crosstalk with bone, adipose tissue and brain.Nature reviews. Endocrinology · 2023Review
- IMPACT OF GRAVES' DISEASE AND ANTITHYROID DRUG THERAPY ON BONE MINERAL DENSITY - PATHOPHYSIOLOGICAL MECHANISMS AND CLINICAL RELEVANCE.Acta clinica Croatica · 2022Review
- The role of IL-6 and osteoprotegerin in bone metabolism in patients with Graves' disease.Turkish journal of medical sciences · 2022Article
- Endocrine Regulation on Bone by Thyroid.Frontiers in endocrinology · 2022Review
- Thyrotropin, Hyperthyroidism, and Bone Mass.The Journal of clinical endocrinology and metabolism · 2021Review
- The Effect of Recombinant Human TSH on Sclerostin and Other Selected Bone Markers in Patients after Total Thyroidectomy for Differentiated Thyroid Cancer.Journal of clinical medicine · 2021Article
- Commonly Prescribed and Over-the-Counter Drugs as Secondary Causes of Osteoporosis-Part Two.Integrative medicine (Encinitas, Calif.) · 2021Article
- Skeletal health in patients with differentiated thyroid carcinoma.Journal of endocrinological investigation · 2021Review
- Endocrine Regulation of Extra-skeletal Organs by Bone-derived Secreted Protein and the effect of Mechanical Stimulation.Frontiers in cell and developmental biology · 2021Review
- Influence of General Mineral Condition on Collagen-Guided Alveolar Crest Augmentation.Materials (Basel, Switzerland) · 2020Article
- Crosstalk of Brain and Bone-Clinical Observations and Their Molecular Bases.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWe have shown that thyroid-stimulating hormone (TSH) has a direct inhibitory effect on osteoclastic bone resorption and that TSH receptor (TSHR) null mice display osteoporosis. To determine the stage of osteoclast development at which TSH may exert its effect, we examined the influence of TSH and agonist TSHR antibodies (TSHR-Ab) on osteoclast differentiation from murine embryonic stem (ES) cells to gain insight into bone remodeling in hyperthyroid Graves' disease.
methodsOsteoclast differentiation was initiated in murine ES cell cultures through exposure to macrophage colony stimulation factor, receptor activator of nuclear factor кB ligand, vitamin D, and dexamethasone.
resultsTartrate resistant acid phosphatase (TRAP)-positive osteoclasts formed in ~12 days. This coincided with the expected downregulation of known markers of self renewal and pluripotency (including Oct4, Sox2, and REX1). Both TSH and TSHR-Abs inhibited osteoclastogenesis as evidenced by decreased development of TRAP-positive cells (~40%-50% reduction, p = 0.0047), and by decreased expression, in a concentration-dependent manner, of osteoclast differentiation markers (including the calcitonin receptor, TRAP, cathepsin K, matrix metallo-proteinase-9, and carbonic anhydrase II). Similar data were obtained using serum immunoglobulin-Gs (IgGs) from patients with hyperthyroid Graves' disease and known TSHR-Abs. TSHR stimulators inhibited tumor necrosis factor-alpha mRNA and protein expression, but increased the expression of osteoprotegerin (OPG), an antiosteoclastogenic human soluble receptor activator of nuclear factor кB ligand receptor. Neutralizing antibody to OPG reversed the inhibitory effect of TSH on osteoclast differentiation evidencing that the TSH effect was at least in part mediated by increased OPG.
conclusionThese data establish ES-derived osteoclastogenesis as an effective model system to study the regulation of osteoclast differentiation in early development. The results support the observations that TSH has a bone protective action by negatively regulating osteoclastogenesis. Further, our results implicate TSHR-Abs in offering skeletal protection in hyperthyroid Graves' disease, even in the face of high thyroid hormone and low TSH levels.
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Registered trials
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