Hypergravity and microgravity exhibited reversal effects on the bone and muscle mass in mice

Tsukasa Tominari,Keita Taniguchi,Kenta Watanabe,Yoshifumi Itoh,Michiko Hirata,Ryota Ichimaru,Akane Yumoto,Chiho Matsumoto,Masaki Shirakawa,Dai Shiba,Chisato Miyaura,Masaki Inada

doi:10.1038/s41598-019-42829-z

Tsukasa Tominari, Keita Taniguchi + Show 10 more

Open Access

https://doi.org/10.1038/s41598-019-42829-z

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Abstract

Spaceflight is known to induce severe systemic bone loss and muscle atrophy of astronauts due to the circumstances of microgravity. We examined the influence of artificially produced 2G hypergravity on mice for bone and muscle mass with newly developed centrifuge device. We also analyzed the effects of microgravity (mostly 0G) and artificial produced 1G in ISS (international space station) on mouse bone mass. Experiment on the ground, the bone mass of humerus, femur and tibia was measured using micro-computed tomography (μCT), and the all bone mass was significantly increased in 2G compared with 1G control. In tibial bone, the mRNA expression of bone formation related genes such as Osx and Bmp2 was elevated. The volume of triceps surae muscle was also increased in 2G compared with 1G control, and the mRNA expression of myogenic factors such as Myod and Myh1 was elevated by 2G. On the other hand, microgravity in ISS significantly induced the loss of bone mass on humerus and tibia, compared with artificial 1G induced by centrifugation. Here, we firstly report that bone and muscle mass are regulated by the gravity with loaded force in both of positive and negative on the ground and in the space.

Highlights

Long-term exposure of microgravity by spaceflight and bed rest on the ground result in severe osteoporosis and muscle atrophy whereas mechanical loading by exercise recover the bone and muscle mass[1,2]
We newly developed a gondola-type centrifuge with a 1.0 m arm to analyze hypergravity-induced the changes of bone and muscle mass
The data showed that the 2G hypergravity for 2 weeks induced muscle hypertrophy via the upregulation of myogenic genes and the down regulation of muscle-specific ubiquitin ligases and autophagy-related genes

Summary

Introduction

Long-term exposure of microgravity (μG) by spaceflight and bed rest on the ground result in severe osteoporosis and muscle atrophy whereas mechanical loading by exercise recover the bone and muscle mass[1,2]. As the rodent model of mechanical unloading, hindlimb unloading, called as tail suspension, sciatic denervation and cast immobilization, have been used for mimicking μG-induced osteoporosis and muscle atrophy[3,4,5]. Various experiments for microgravity have been performed at the Japanese Experimental Module, called as ‘Kibo’, in the International Space Station (ISS). In 2016, the 1st mouse project in space using mouse habitat unit (MHU) was conducted by JAXA. This project (called as MHU-1) used the Centrifuge-equipped Biological Experiment Facility (CBEF) and provided both microgravity (μG) and artificial 1G in space, and reported that artificial 1G in space mostly cancelled the bone loss and muscle atrophy due to μG25. In 2017, the 2nd mouse space project (called as MHU-2) was performed, and we analyzed bone mass in the detail in the space

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