RESEARCH

Research Overview

In space, living organisms are exposed to environments that differ dramatically from those on Earth, including microgravity, cosmic radiation, and confined habitats. These conditions affect a wide range of physiological systems, including the skeletal, muscular, immune, and cardiovascular systems, and represent major medical challenges for long-duration space missions.

The Space Biomedical Science Research Group aims to elucidate the mechanisms underlying biological responses to the space environment at the molecular, cellular, and organismal levels. Our research focuses particularly on bone metabolism and tissue remodeling, investigating how changes in gravity influence cellular functions and tissue homeostasis.

Using model organisms such as medaka fish and mice, we conduct fundamental biological research while also participating in spaceflight and artificial-gravity experiments to better understand the mechanisms by which living organisms adapt to space environments.

Furthermore, bone loss and muscle dysfunction observed in astronauts share important characteristics with osteoporosis, frailty, and physical decline associated with prolonged bed rest on Earth. We seek to extend these findings to the oral and craniofacial fields, with the goal of advancing research on alveolar and craniofacial bone metabolism, oral function, swallowing function, and tissue regeneration.

Our research is expected to contribute not only to maintaining astronaut health during future lunar and Martian exploration missions, but also to improving our understanding of and developing new approaches for medical challenges on Earth, including osteoporosis, age-related disorders, and functional decline associated with long-term immobilization.

Osteoclasts Act as Gravity Sensors

We revealed that osteoclasts can directly sense hypergravity and respond by rapidly reorganizing their actin cytoskeleton, leading to reduced bone resorption activity (Takahashi N, et al, PLOS One. 2026 In Press).

Periostin Regulates Bone and Dental Health During Aging

Periostin is an extracellular matrix protein that is highly expressed in tissues supporting bones and teeth. In this study, we investigated age-related changes in skeletal and dental tissues using periostin-deficient mice.

We found that the absence of periostin led to progressive dental abnormalities with aging, including altered tooth morphology and enamel defects, accompanied by changes in craniofacial morphology. In addition, while normal mice exhibited age-related bone loss, periostin-deficient mice showed abnormal bone remodeling and developed ectopic bone formation in regions such as around the knee joint.

These findings demonstrate that periostin plays a critical role not only in maintaining the structural integrity of bones and teeth but also in preserving normal bone remodeling during aging. Our study highlights the importance of periostin in skeletal and dental health and suggests its potential involvement in age-related bone and tooth disorders (Fujita et al, J Oral Biosci, 68(1):100734. 2026).

Gravity Regulates Bone Formation in Developing Medaka

In this study, we investigated the effects of altered gravity on bone formation using medaka larvae. We found that hypergravity promoted osteoblast activity and induced changes in the mineralization of bones and teeth, demonstrating that gravity plays an important role in regulating skeletal development during early life stages.

These findings provide evidence that the gravity environment influences bone formation and mineralization during development. Our work also highlights the value of medaka as a powerful model organism for studying skeletal biology in space and for understanding the effects of altered gravity on vertebrate tissues (Takahashi et al, Biological Sciences in Space, 35, 24-31, 2021).

Long-Term Medaka Experiment Aboard the International Space Station

Life on Earth has evolved under the constant influence of gravity. As humans began traveling into space, it became evident that prolonged exposure to microgravity leads to a reduction in bone density, highlighting the importance of gravity for maintaining skeletal health. To investigate the role of gravity in living organisms, we utilized medaka fish, a well-established model for bone research, and the microgravity environment of the International Space Station (ISS).

As part of a collaborative project led by Professor Akira Kudo (Tokyo Institute of Technology), we conducted a two-month medaka breeding experiment aboard the Japanese Experiment Module Kibo on the ISS. The image shows medaka swimming inside the space habitat. One fish, indicated by the red arrow, is swimming upside down, demonstrating the absence of a fixed sense of up and down in microgravity—much like astronauts floating freely in space. In fact, the fish were featured in Smithsonian Magazine and affectionately referred to as “fishonauts.”

By analyzing the skeletons of medaka raised in space, we revealed that activation of osteoclasts, the cells responsible for bone resorption, is one of the factors contributing to spaceflight-induced bone loss. These findings provided important insights into the mechanisms underlying skeletal adaptation to microgravity and advanced our understanding of bone metabolism in space (Chatani et al., Sci Rep, 5, 14172, 2015).

Real-Time Observation of Bone Cells in Space

To investigate how bone cells respond when organisms transition from Earth's gravity to microgravity, we conducted an eight-day spaceflight experiment using medaka larvae aboard the International Space Station (ISS). In this project, led by Professor Akira Kudo (Tokyo Institute of Technology), the fish were observed in real time from Earth throughout the mission.

This study represented the world's first attempt to remotely operate a microscope aboard the ISS from the ground, enabling continuous live imaging of biological processes in space. Through these observations, we discovered that exposure to microgravity rapidly induced significant changes in the expression of genes associated with bone cells (Chatani et al., Scientific Reports 6, 39545, 2016).

These findings provided the first direct evidence that bone cells respond quickly to the space environment at the molecular level. Building on these results, we continue to investigate the mechanisms by which altered gravity regulates bone metabolism and skeletal homeostasis (Chatani et al., Sci Rep, 6, 39545, 2016).

Live Imaging of Osteoclasts in a Transgenic Medaka Model

Bone is continuously remodeled through the coordinated actions of osteoblasts, which form bone, and osteoclasts, which resorb it. Osteoclasts possess the remarkable ability to selectively remove unnecessary bone while preserving surrounding skeletal structures. However, the mechanisms by which osteoclasts recognize and target specific sites for bone resorption remain poorly understood.

To address this question, we developed a transgenic medaka model that enables the visualization of osteoclasts in living animals. In this model, osteoclasts are labeled with enhanced green fluorescent protein (EGFP) under the control of the TRAP promoter, a marker strongly expressed in osteoclasts. By combining this system with red fluorescent labeling of bone tissue, we can simultaneously visualize osteoclasts and skeletal structures in vivo and in real time.

This model allows us to track osteoclast migration, localization, and bone-resorbing activity at the whole-organism level. We are currently investigating how interactions with osteoblasts, blood vessels, and the surrounding microenvironment contribute to the positioning and function of osteoclasts during bone remodeling.

Our research provides a unique platform for uncovering the fundamental principles governing bone remodeling and may contribute to the development of novel therapeutic strategies for skeletal disorders, including osteoporosis (Chatani et al, Dev Biol, 360(1):96-109. 2011).

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