[Neurovascular & interorgan network/ MHU-7]
Elucidating the underlying mechanism of age-related musculoskeletal disorders from the viewpoint of inter-organ communication network

RESEARCH OVERVIEW

• In the microgravity environment of space, the aging process is accelerated faster than on Earth, but the mechanism of age-related disorders is not well understood. It has been shown that the projection of sensory nerves and blood vessels into bone is important for maintaining bone mass. It has also been found that mice with impaired sensory nerves had markedly suppressed recovery from bone and skeletal muscle damage, suggesting that the neuro-vascular network plays an important role in maintaining musculoskeletal homeostasis. The Elucidating the Underlying Mechanism of Age-related Musculoskeletal Disorders from the Viewpoint of Inter-organ Communication Network (Mouse Habitat Unit-7 or MHU-7) study seeks to provide clarification of the role of the neuro-vascular network in the onset or progress of age-related musculoskeletal disorders using space experiments.
• In addition, since the age-related functional decline of the musculoskeletal system is associated with deterioration of various organs, it is important to understand changes in the pathology of the whole individual. The study also focuses on secretory microRNA (miRNA), which is known as an inter-organ communication factor.The aim is to identify serum secretory miRNAs whose expression is specifically altered by gravity change or aging, and to better understand the mechanisms of age-related functional deterioration of the whole individual from the viewpoint of an inter-organ communication network.

SPACE APPLICATIONS

The Space Application for this investigation has yet to be identified.

EARTH APPLICATIONS

By making the best use of a space investigations that focuses on the neuro-vascular system and secretory microRNAs (miRNAs), this research can contribute to a better understanding of the novel mechanisms of mechanical stress sensing and age-related changes of muscles and bones. Moreover, the identification of miRNAs that fluctuate with changes in gravity can contribute to the clarification of the pathogenic mechanism of systemic diseases caused by aging and being bedridden, as well as to the development of novel biomarkers that predict the onset of age-related diseases and new therapeutic interventions to these diseases.

OPERATIONAL REQUIREMENTS AND PROTOCOLS

Genetically modified mice (Sox10-Venus mice), in which the green fluorescent protein Venus is expressed in the nerves, are launched to the International Space Station and reared in the Kibo Japanese Experiment Module using JAXA Habitat Cage Units. Comparative analyses with the ground control group are carried out using 3D structural analysis of nerves and blood vessels in muscle and bone tissues using a novel tissue optical clearing technology, histological and molecular biological analysis of musculoskeletal tissues, and comprehensive expression analysis of serum secretory microRNAs.

SATO Shingo [Tokyo Medhical and Dental University]