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尽管表达增加,但30天的太空飞行并未改变小鼠颅骨结构。

Thirty days of spaceflight does not alter murine calvariae structure despite increased expression.

作者信息

Macaulay Timothy R, Siamwala Jamila H, Hargens Alan R, Macias Brandon R

机构信息

University of California, San Diego, UCSD Medical Center, Orthopaedic Surgery Department, 350 Dickinson Street, Suite 121, Mail Code 8894, San Diego, CA 92103-8894, USA.

University of California, San Diego, Altman Clinical and Translational Research Institute, Lower Level 2 West 417, 9452 Medical Center Drive, La Jolla, CA 92037, USA.

出版信息

Bone Rep. 2017 Aug 18;7:57-62. doi: 10.1016/j.bonr.2017.08.004. eCollection 2017 Dec.

Abstract

Previously our laboratory documented increases in calvaria bone volume and thickness in mice exposed to 15 days of spaceflight aboard the NASA Shuttle mission STS-131. However, the tissues were not processed for gene expression studies to determine what bone formation pathways might contribute to these structural adaptations. Therefore, this study was designed to investigate both the structural and molecular changes in mice calvariae after a longer duration of spaceflight. The primary purpose was to determine the calvaria bone volume and thickness of mice exposed to 30 days of spaceflight using micro-computed tomography for comparison with our previous findings. Because sclerostin, the secreted glycoprotein of the gene, is a potent inhibitor of bone formation, our second aim was to quantify mRNA expression using quantitative PCR. Calvariae were obtained from six mice aboard the Russian 30-day Bion-M1 biosatellite and seven ground controls. In mice exposed to 30 days of spaceflight, calvaria bone structure was not significantly different from that of their controls (bone volume was about 5% lower in spaceflight mice, p = 0.534). However, mRNA expression was 16-fold (16.4 ± 0.4, p < 0.001) greater in the spaceflight group than that in the ground control group. Therefore, bone formation may have been suppressed in mice exposed to 30 days of spaceflight. Genetic responsiveness (e.g. sex or strain of animals) or in-flight environmental conditions other than microgravity (e.g. pCO levels) may have elicited different bone adaptations in STS-131 and Bion-M1 mice. Although structural results were not significant, this study provides biochemical evidence that calvaria mechanotransduction pathways may be altered during spaceflight, which could reflect vascular and interstitial fluid adaptations in non-weight bearing bones. Future studies are warranted to elucidate the processes that mediate these effects and the factors responsible for discordant calvaria bone adaptations between STS-131 and Bion-M1 mice.

摘要

此前,我们实验室记录了搭乘美国国家航空航天局(NASA)STS - 131航天飞机任务进行15天太空飞行的小鼠颅骨骨体积和厚度增加。然而,这些组织未进行基因表达研究,以确定哪些骨形成途径可能导致这些结构适应性变化。因此,本研究旨在调查更长时间太空飞行后小鼠颅骨的结构和分子变化。主要目的是使用微计算机断层扫描确定暴露于30天太空飞行的小鼠的颅骨骨体积和厚度,以便与我们之前的研究结果进行比较。由于sclerostin基因分泌的糖蛋白是骨形成的有效抑制剂,我们的第二个目标是使用定量PCR对sclerostin mRNA表达进行定量。从搭乘俄罗斯30天Bion - M1生物卫星的6只小鼠和7只地面对照小鼠获取颅骨。在暴露于30天太空飞行的小鼠中,颅骨结构与对照小鼠无显著差异(太空飞行小鼠的骨体积约低5%,p = 0.534)。然而,太空飞行组的sclerostin mRNA表达比地面对照组高16倍(16.4±0.4,p < 0.001)。因此,暴露于30天太空飞行的小鼠的骨形成可能受到抑制。遗传反应性(如动物的性别或品系)或微重力以外的飞行环境条件(如pCO水平)可能在STS - 131和Bion - M1小鼠中引发了不同的骨适应性变化。尽管结构结果不显著,但本研究提供了生化证据,表明太空飞行期间颅骨机械转导途径可能发生改变,这可能反映了非承重骨中血管和组织液的适应性变化。有必要进行进一步研究,以阐明介导这些效应的过程以及导致STS - 131和Bion - M1小鼠颅骨骨适应性不一致的因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/775f/5574818/7b9a2654c4d7/gr1.jpg

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