Saxena Ritu, Pan George, McDonald Jay M
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Ann N Y Acad Sci. 2007 Nov;1116:494-8. doi: 10.1196/annals.1402.033. Epub 2007 Jul 26.
Prolonged microgravity experienced by astronauts is associated with a decrease in bone mineral density. To investigate the effect of microgravity on differentiation of osteoclasts and osteoblasts, we used a NASA-recommended, ground-based, microgravity-simulating system, the Rotary Cell Culture System (RCCS). Using the RCCS, we demonstrated that modeled microgravity (MMG) inhibited osteoblastogenesis and increased adipocyte differentiation in human mesenchymal stem cells incubated under osteogenic conditions. This transformation involves reduced RhoA activity and cofilin phosphorylation, disruption of F-actin stress fibers, and decreased integrin signaling through focal adhesion kinase. We have used the system to show that MMG also stimulates osteoclastogenesis. These systems provide the opportunity to develop pharmacological agents that will stimulate osteoblastogenesis and inhibit osteoclastogenesis.
宇航员所经历的长期微重力与骨矿物质密度降低有关。为了研究微重力对破骨细胞和成骨细胞分化的影响，我们使用了美国国家航空航天局（NASA）推荐的基于地面的微重力模拟系统——旋转细胞培养系统（RCCS）。利用RCCS，我们证明了模拟微重力（MMG）在成骨条件下培养的人间充质干细胞中抑制成骨细胞生成并增加脂肪细胞分化。这种转变涉及RhoA活性降低和丝切蛋白磷酸化减少、F-肌动蛋白应力纤维的破坏以及通过粘着斑激酶的整合素信号传导减少。我们利用该系统表明MMG也刺激破骨细胞生成。这些系统为开发能刺激成骨细胞生成并抑制破骨细胞生成的药物提供了机会。
