Microgravity promotes osteoclast activity in medaka fish reared at the international space station.

Masahiro Chatani,Akiko Mantoku,Keiichi Ohya,Hiromi Suzuki,Yasutaka Sugamori,Toru Sakimura,Yoshiro Takano,Masaki Shirakawa,Kazuhiro Takeyama,Fumiaki Tanigaki,Dawud Abduweli,Yasushi Kono,Akira Kudo,Kazuhiro Aoki,Satoko Uchida

doi:10.1038/srep14172

Abstract

The bone mineral density (BMD) of astronauts decreases specifically in the weight-bearing sites during spaceflight. It seems that osteoclasts would be affected by a change in gravity; however, the molecular mechanism involved remains unclear. Here, we show that the mineral density of the pharyngeal bone and teeth region of TRAP-GFP/Osterix-DsRed double transgenic medaka fish was decreased and that osteoclasts were activated when the fish were reared for 56 days at the international space station. In addition, electron microscopy observation revealed a low degree of roundness of mitochondria in osteoclasts. In the whole transcriptome analysis, fkbp5 and ddit4 genes were strongly up-regulated in the flight group. The fish were filmed for abnormal behavior; and, interestingly, the medaka tended to become motionless in the late stage of exposure. These results reveal impaired physiological function with a change in mechanical force under microgravity, which impairment was accompanied by osteoclast activation.

Highlights

International Space Station (ISS), several genes in the downstream of the glucocorticoid receptor (GR)[9] were strongly up-regulated in the flight group
We investigated alteration of osteoclast potency between the flight medaka group and the ground control in terms of osteoclast volume calculated from the green fluorescent signals in osteoclasts, anti-GFP antibody-positive area by immunostaining, and enzymatic activity by tartrate-resistant acid phosphatase (TRAP) staining
The number of multinucleate osteoclasts was increased in the flight medaka at day 56, whereas the total number of nuclei in GFP-positive cells showed no significant difference, indicating that osteoclast differentiation was not enhanced but that the osteoclast fusion process was promoted under microgravity during the 56-day period

Summary

Introduction

ISS, several genes in the downstream of the glucocorticoid receptor (GR)[9] were strongly up-regulated in the flight group. In the flight fish group at day 56, the calcified area (white signals) in the pharyngeal bone region was decreased, compared with that for the ground control (Fig. 2B,C); whereas there was no significant difference in calcification at day[14] (Supplementary Fig. 2). The osteoclast volume was normalized by the osteoblast volume, because the sizes of pharyngeal bones varied, with the result being that the relative ratio of the GFP volume divided by the DsRed volume was increased during flight (Fig. 3G,H).

Results

Conclusion