THE TEMPORAL RESPONSE OF BONE TO UNLOADING
THE TEMPORAL RESPONSE OF BONE TO UNLOADING
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DOI：
10.1210/endo-118-2-733
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发表时间：
1986-02-01
期刊：
影响因子：
4.8
通讯作者：
MOREYHOLTON, E
中科院分区：
文献类型：
--
作者：
GLOBUS, RK;BIKLE, DD;MOREYHOLTON, E
一种失重模型，在这种模型中，大鼠的后肢以40度的角度用尾巴抬起。在保持前肢正常承重的同时，后肢卸载的角度已被用来模拟某些太空飞行条件。当我们在生长中的大鼠身上使用这个模型时，我们发现后肢和腰椎的骨重增长在一周后停止，而前肢和颈椎的骨重增长没有受到影响。然而，在2周内，尽管持续的骨骼卸载，后肢和腰椎的骨重增加恢复到正常。由于生长期大鼠的骨量主要由骨形成决定(骨吸收程度适中)，我们用放射性同位素掺入法(用~(45)Ca和[~3H]Pro)和组织形态计量学(用四环素标记)研究了选择性骨骼卸载对后肢抬高2周期间骨形成的影响。放射性同位素掺入的研究表明，在骨骼卸载的第五天，骨形成受到抑制。到第10~12天，骨形成已恢复正常。与皮质骨相比，松质骨(腰椎和胫骨近端)含有更多的~(45)Ca和[~3H]Pro(表明更大的代谢活性)，对骨骼卸载有更大的绝对响应。这些研究的结果通过三四环素标记骨形成的组织形态计量学测量得到了证实。我们得出的结论是，这种模拟失重的模型导致了卸载骨的骨形成最初受到抑制。这种暂时的骨形成停止之后是骨重量的增加停止，然后在14天后恢复到正常的速度，尽管骨骼继续卸载。我们认为，这种抑制和恢复骨形成的循环对于理解太空飞行、固定或卧床休息期间的骨动力学具有深远的意义，并为研究调节骨形成的激素和机械因素提供了机会。
A model of weightlessness in which the hindlimbs of rats were elevated by their tails at a 40.degree. angle to unload the hindlimbs while maintaining normal weight bearing on the forelimbs has been used to simulate certain conditions of space flight. When we used this model in growing rats, we found that growth in bone weight ceased by 1 week in the hindlimbs and lumbar vertebrae, whereas growth in bone weight in the forelimbs and cervical vertebrae remained unaffected. Within 2 weeks, however, the accretion of bone weight in the hindlimbs and lumbar vertebrae returned to normal despite continued skeletal unloading. Since bone weight in the growing rat is primarily determined by bone formation (bone resorption is modest), we investigated the effects of selective skeletal unloading on bone formation during 2 weeks of hindlimb elevation using radioisotope incorporation (with 45Ca and [3H]proline) and histomorphometry (with tetracycline labeling). The studies using radioisotope incorporation showed that bone formation was inhibited by the fifth day of skeletal unloading. By the 10th to 12th day, bone formation had returned toward normal. In comparison with cortical bone, cancellous bone (lumbar vertebrae and proximal tibiae) incorporated more 45Ca and [3H]proline (indicating greater metabolic activity) and had a greater absolute response to skeletal unloading. The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. We conclude that this model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed by a cessation in the accretion of bone weight, which then resumes at a normal rate by 14 days despite continued skeletal unloading. We believe that this cycle of inhibition and resumption of bone formation has profound implications for understanding bone dynamics during space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.