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

准微重力引起的骨代谢变化及其骨代谢剂的恢复。

• 批准号: 12672177
• 负责人: KAWASHIMA Kohtaro
• 金额: $ 2.11万
• 依托单位: TEIKYO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672177/
• 关键词: OUASI-MICROGRAVITY; OSTEOBLASTS; ALKALINE PHOSPHATASE; OSTEOCALCIN; VITAMIN D3; CYTOSKELETON; CYTOCHALASINB; cAMP; 微小重力環境; クリノスタット培養; クメステロール類縁体(KCA-098); 1α、25-(OH)_2D_3; 低重力環境; 高重力環境

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.

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。因此，了解骨破坏的机制和克服这种情况的药物是很重要的。本研究通过研究准微重力对成骨细胞的影响，推断空间微重力对成骨细胞的影响。恒温培养产生的准微重力使成骨细胞碱性磷酸酶活性暂时降低，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，骨腔内骨矿物质密度的降低似乎取决于骨形成的时间减少和骨吸收的持续增加。活性维生素D3, 1 α,25-(OH)2D3处理可恢复碱性磷酸酶活性的暂时下降，提示1 α，25-(OH)2D3对骨疾病具有活性，即使是在空间。准微重力暴露诱导的骨钙素合成增加在很大程度上被肌动蛋白丝破坏剂细胞松弛素B的处理所抑制，说明细胞骨架，尤其是肌动蛋白丝对骨钙素的诱导具有重要作用。然而，细胞松弛素b处理对碱性磷酸酶活性的降低没有影响。准微重力导致细胞内cAMP含量升高。细胞松弛素b处理对细胞内cAMP含量的增加没有影响，表明肌动蛋白纤维不参与准微重力诱导的细胞内cAMP含量的增加和碱性磷酸酶活性的降低。现在，我将分析cAMP、细胞骨架和成骨细胞功能之间的网络系统，包括骨钙素合成和碱性吞噬酶活性。

项目成果

Mio Furutsu: "Bidirectional effects of hypergravity on the cell growth and differentiated functions of osteoblast-like ROS 17/2.8 cells"Biol.Pharm.Bull.. 23(10). 1258-1261 (2000)

Mio Furutsu：“超重力对成骨细胞样 ROS 17/2.8 细胞生长和分化功能的双向影响”Biol.Pharm.Bull.. 23(10)。

Mio Furutsu: "Bidirectional effects of hypergravity on the growth and differentiated functions of osteoblast-like ROS17/2.8 cells"Biol.Pharm.Bull.. 23(2). 1258-1261 (2000)

Mio Furutsu：“超重力对成骨细胞样 ROS17/2.8 细胞生长和分化功能的双向影响”Biol.Pharm.Bull.. 23(2)。

M. FURUTSU: "Bidirectional effects of hypergravity on the cell growth and differentiated functions of osteoblast-like ROS17/2.8 cells"Biol. Pharm. Bull.. 23(10). 1258-1261 (2000)

M. FURUTSU：“超重力对成骨细胞样 ROS17/2.8 细胞生长和分化功能的双向影响”Biol。

Mio Furutsu: "Bidirectional effects of hypergravity on the growth and differentiated functions of osteoblast-like ROS17/2.8 cells"Biol. Pharm. Bull.. 23(2). 1258-1261 (2000)

Mio Furutsu：“超重力对成骨细胞样 ROS17/2.8 细胞生长和分化功能的双向影响”Biol。