Prostaglandin-Independent Stimulation of Bone Resorption in Mouse Calvariae and in Isolated Rat Osteoclasts by Thyroid Hormones (T 4,and T 3 )

Abstract

The thyroid hormones, thyroxine (T₄) and triiodothyronine (T₃), were found to enhance both neonatal mouse calvarial bone resorption and pit formation on bovine slices by isolated rat osteoclasts. Dosage-dependent release of ⁴⁵Ca from mouse calvarial bones was observed after 120 hr of culture with 10^–6-10^–8 MT₄ and 10^–6-10^–10 MT₃. Maximum treatment/control ratios of ⁴⁵Ca release were recorded for 10^–7 MT₄ and 10^–8 MT₃. Inhibition of ⁴⁵Ca release stimulated by 10^–8 MT₃ was observed in the presence of 30 nM salmon calcitonin at 48 hr and 120 hr of culture with no indication of “escape” by T₃-treated bones. In contrast, stimulation of ⁴⁵Ca release from mouse calvarial bones by 10^–7 MT₄ and 10^–8 MT₃ was not inhibited by 10^–6 M indomethacin. Formation of PGE₂ and PGI₂ (evaluated by measuring 6-keto-PGF_1α) by mouse calvariae was also not increased by 10^–8 MT₃ after 120 hr of culture. Furthermore, no increases in cAMP formation were observed in calvarial bone cultures after either 10 min or 24 hr of exposure to 10^–8 MT₃. However, significant inhibition of ⁴⁵Ca release stimulated by 10^–8 MT₃ was found at 120 hr in the presence of 10^–3 M hydroxyurea. When isolated rat osteoclasts were cultured in the presence of 10^–7 MT₃, a 1.4-fold stimulation of pit number was observed. Pit formation was not affected by addition of 10^–6 M indomethacin to either the control or T₃-treated cultures. These data suggest that the stimulation of bone resorption in neonatal mouse calvariae and activation of isolated rat osteoclasts by the thyroid hormones is not related to either prostaglandin or cAMP formation. In mouse calvariae, the effect on bone resorption of the thyroid hormones is dependent on increased cellular replication, perhaps of osteoclast precursors, or other bone cells involved in the resorptive process.