Conaway H H, Ransjö M, Lerner U H
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Proc Soc Exp Biol Med. 1998 Feb;217(2):153-61. doi: 10.3181/00379727-217-44217.
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) M T3. Maximum treatment/control ratios of 45Ca release were recorded for 10(-7) M T4 and 10(-8) MT3. Inhibition of 45Ca release stimulated by 10(-8) M T3 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-PGF1alpha) 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) M T3 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.
甲状腺激素，即甲状腺素（T4）和三碘甲状腺原氨酸（T3），被发现可增强新生小鼠颅骨的骨吸收以及分离的大鼠破骨细胞在牛切片上形成的陷窝。在用10(-6)-10(-8) M T4和10(-6)-10(-10) M T3培养120小时后，观察到小鼠颅骨中45Ca呈剂量依赖性释放。对于10(-7) M T4和10(-8) M T3，记录到了45Ca释放的最大处理/对照比值。在培养48小时和120小时时，在30 nM鲑鱼降钙素存在的情况下，观察到10(-8) M T3刺激的45Ca释放受到抑制，且T3处理的骨骼没有“逃逸”迹象。相比之下，10(-6) M吲哚美辛并未抑制10(-7) M T4和10(-8) M T3对小鼠颅骨45Ca释放的刺激。培养120小时后，10(-8) M T3也未增加小鼠颅骨中PGE2和PGI2（通过测量6-酮-PGF1α评估）的形成。此外，在暴露于10(-8) M T3 10分钟或24小时后，颅骨培养物中未观察到cAMP形成增加。然而，在10(-3) M羟基脲存在的情况下，在120小时时发现10(-8) M T3刺激的45Ca释放受到显著抑制。当在10(-7) M T3存在的情况下培养分离的大鼠破骨细胞时，观察到陷窝数量有1.4倍的增加。向对照或T3处理的培养物中添加10(-6) M吲哚美辛对陷窝形成没有影响。这些数据表明，甲状腺激素对新生小鼠颅骨骨吸收的刺激以及对分离的大鼠破骨细胞的激活与前列腺素或cAMP的形成均无关。在小鼠颅骨中，甲状腺激素对骨吸收的作用依赖于细胞复制的增加，可能是破骨细胞前体或参与吸收过程的其他骨细胞的复制增加。
