Disuse in adult male rats attenuates the bone anabolic response to a therapeutic dose of parathyroid hormone.
Disuse in adult male rats attenuates the bone anabolic response to a therapeutic dose of parathyroid hormone.
复制标题
成年雄性大鼠的废弃会减弱对治疗剂量的甲状旁腺激素的骨合成代谢反应。
DOI：
10.1152/japplphysiol.01622.2005
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Morey-Holton,Emily
中科院分区：
文献类型：
--
作者：
Turner,RussellT;Lotinun,Sutada;Hefferan,TheresaE;Morey-Holton,Emily
间歇性甲状旁腺激素(PTH)治疗增加后肢去负荷(HLU)大鼠的骨形成和防止骨丢失。然而，甲状旁腺激素的作用机制尚不完全清楚。为了探讨负重和甲状旁腺激素之间可能的相互作用，我们用人治疗量(1μg·kg−1·day−1)的人甲状旁腺素(1-34)(HPTH)处理6月龄负重和HLU大鼠。皮质骨和松质骨的形成分别在胫骨-腓骨融合的骨干近端和干骺端的近端被测量。两周的后肢卸载导致两个骨骼部位的骨形成速度显著降低，这一点仅在松质部位应用甲状旁腺素治疗可以防止。相反，PTH治疗增加了负重大鼠皮质骨和松质骨的形成。双因素方差分析显示，hPTH和hLU对骨形成的所有组织形态计量学指标[矿物质沉积率(MAR)、双标周长(DLPm)和骨形成率(BFR)]具有独立和相反的影响。负重和hPTH对皮质部位的dLPm和BFR的骨合成代谢的影响是相加的，对松质部位的MAR也是如此。相反，负重和hPTH导致皮质骨MAR和松质骨dLPm和BFR协同增加。结论：负重和甲状旁腺素通过导致成骨细胞数量和活性指数的部位特异性相加和协同增加而协同作用，提示针对骨质疏松部位的负重运动可提高甲状旁腺素治疗骨质疏松症的疗效。
Intermittent treatment with parathyroid hormone (PTH) increases bone formation and prevents bone loss in hindlimb-unloaded (HLU) rats. However, the mechanisms of action of PTH are incompletely known. To explore possible interactions between weight bearing and PTH, we treated 6-mo-old weight-bearing and HLU rats with a human therapeutic dose (1 μg·kg−1·day−1) of human PTH(1–34) (hPTH). Cortical and cancellous bone formation was measured in tibia at the diaphysis proximal to the tibia-fibula synostosis and at the proximal metaphysis, respectively. Two weeks of hindlimb unloading resulted in a dramatic decrease in the rate of bone formation at both skeletal sites, which was prevented by PTH treatment at the cancellous site only. In contrast, PTH treatment increased cortical as well as cancellous bone formation in weight-bearing rats. Two-way ANOVA revealed that hPTH and HLU had independent and opposite effects on all histomorphometric indexes of bone formation [mineral apposition rate (MAR), double-labeled perimeter (dLPm), and bone formation rate (BFR)] at both skeletal sites. The bone anabolic effects of weight bearing and hPTH on dLPm and BFR at the cortical site were additive, as were the effects on MAR at the cancellous site. In contrast, weight bearing and hPTH resulted in synergistic increases in cortical bone MAR and cancellous bone dLPm and BFR. We conclude that weight bearing and PTH act cooperatively to increase bone formation by resulting in site-specific additive and synergistic increases in indexes of osteoblast number and activity, suggesting that weight-bearing exercise targeted to osteopenic skeletal sites may improve the efficacy of PTH therapy for osteoporosis.