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Endocrine Abstracts (2014) 34 OC4.4 | DOI: 10.1530/endoabs.34.OC4.4

SFEBES2014 Oral Communications Thyroid and bone (6 abstracts)

Thyroid hormones stimulate osteoclastogenesis via TRα-dependent actions in osteoblasts

John G Logan , J H Duncan Bassett & Graham R Williams

Imperial College London, London, UK.

Thyrotoxicosis results in osteoporosis and thyroid hormone (T3) stimulates osteoclastic bone resorption by unknown mechanisms. We previously demonstrated that knockout mice lacking thyroid hormone receptor α (TRα0/0) are euthyroid but have high bone mass, whereas mice lacking TRβ (TRβ−/−) are thyrotoxic and have osteoporosis. Tartrate resistant acid phosphatase (TRAcP) staining revealed osteoclast numbers were reduced by 13% (P<0.05) in TRα0/0 mice, but increased by 20% (P<0.05) in TRβ−/− mice, suggesting T3 acts via TRα to stimulate osteoclastogenesis and bone resorption.

To test this hypothesis, we stimulated bone marrow (BM) from WT, TRα0/0 and TRβ−/− mice with M-CSF (25 ng/ml) and RANKL (10 ng/ml) in the absence or presence of T3 (100 nM). T3 had no effect on the number, size or survival of osteoclasts of any genotype demonstrating T3 does not exert direct actions in osteoclasts. Despite this, threefold (P<0.001) greater numbers of osteoclasts formed in cultures from TRα0/0 mice compared to WT or TRβ−/−, indicating impaired osteoclast precursor cell differentiation in vivo in TRα0/0 mice. WT, TRα0/0 or TRβ−/− BM was co-cultured with WT osteoblasts in the absence and presence of T3, but without addition of M-CSF and RANKL. There was a 35–66% (P<0.05) increase in osteoclast number and TRAcP activity following T3 treatment in all these co-cultures, indicating impaired osteoclastogenesis in TRα0/0 mice does not result from an osteoclast defect. We next co-cultured WT BM with WT, TRα0/0 or TRβ−/− osteoblasts in the absence or presence of T3. T3 treatment resulted in a 45–68% increase (P<0.01) in osteoclast number and TRAcP activity when WT BM was co-cultured with WT and TRβ−/− osteoblasts. By contrast, few osteoclasts formed in co-cultures of WT BM with TRα0/0 osteoblasts in the absence or presence of T3.

Overall, these data demonstrate that T3 stimulates bone resorption indirectly via TRα-dependent actions in osteoblasts.

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