The changes of bone metabolism induced by quasi-microgravity and its recovery by the bone-metabolizing agents.

骨组织对微重力敏感，导致骨密度降低。在不久的将来，许多人将留在太空中生活。本研究通过研究准微重力对成骨细胞的影响来推测空间微重力的作用，回转器培养产生的准微重力使成骨细胞碱性磷酸酶活性暂时下降，骨钙素合成持续增加。骨钙素被认为是骨吸收的刺激剂。因此，该间隙骨密度的降低可能与骨形成暂时减少和骨吸收持续增加有关。活性维生素D_3，1 α，25-（OH）_2D_3可恢复碱性磷酸酶活性的暂时性下降，提示1 α，25-（OH）_2D_3即使在太空中对骨疾病也有活性。细胞松弛素B（一种肌动蛋白丝的破坏剂）处理可明显抑制准微重力诱导的骨钙素合成的增加，表明细胞骨架尤其是肌动蛋白丝对骨钙素的诱导起重要作用。而细胞松弛素B处理对碱性磷酸酶活性的下降无明显影响。准微重力引起细胞内cAMP含量增加。细胞松弛素B处理也没有改变cAMP的这种增加。这些结果表明，肌动蛋白纤维不参与准微重力引起的细胞内cAMP含量的增加和碱性磷酸酶活性的降低，下面，我将分析cAMP、细胞骨架与成骨细胞功能（包括骨钙素合成和碱性磷酸酶活性）之间的网络系统。

Bone tissues are sensitive to microgravity, leading to the decrease of bone mineral density. Many people are going to stay and live in the space in near future. Therefore, it is important to know the mechanism of bone destruction and to know the drugs to overcome the situation.In this reseach, the effects of quasi-microgravity on the osteoblasts were studied to infer the effect of microgravity in the space.Quasi-microgravity generated by the clinostat culture brought the temporal decrease of alkaline phosphatase activity of osteoblasts, and brought the continued increase of osteocalcine synthesis. Osteocalcine is regarded as the stimulator of bone resorption. Therefore, the decrease of bone mineral density in the space seems to be depend on the temporal decrease of bone formation and the continued increase of bone resorption. The temporal decrease of alkaline phosphatase activity was recovered by the treatment of active vitamin D3, 1 α,25-(OH)2D3, suggesting that 1 α ,25-(OH)2D3 is active for bone deseases even if in the space. The increase of osteocalcine synthesis induced by the exposure of quasi-microgravity was largely inhibited by the treatment of cytochalasin B, a destructive agent of actin filament, indicating that cytoskeleton, especially actin filament, is important for the induction of osteocalcine. However, the decrease of alkaline phosphatase activity was not changed by the treatment of cytochalasin B. Quasi-microgravity caused the increase of intracellular cAMP contents. This increase of cAMP was also not changed by the treatment of cytochalasin B. These results showed that actin fiaments do not participate the increase of intracellular cAMP contents and the decrease of alkaline phosphatase activity induced bu the exposure of quasi-microgravity.Now, I am going to analyze the network system between cAMP, cytoskeleton, and cell function of osteoblasts including osteocalcine synthesis and alkaline phaophatase activity.