Osteocytes and mechano-transduction (Osteo-4) - 11.22.16

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Science Objectives for Everyone
Osteocytes and Mechanomechano-transduction (Osteo-4) studies the effects of microgravity on the function of osteocytes, which are the most common cells in bone. These cells reside within the mineralized bone and can sense mechanical forces, or the lack of them, but researchers do not know how. Osteo-4 allows scientists to analyze changes in the physical appearance and genetic expression of mouse bone cells in microgravity.
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The following content was provided by Paola Divieti Pajevic, MD, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: Osteo-4

Principal Investigator(s)
Paola Divieti Pajevic, MD, Ph.D., Boston, MA, United States

Lisa E. Freed, MD, Ph.D., Charles Stark Draper Laboratory, Cambridge, MA, United States

Calm Technologies Inc., Kingston, Ontario, Canada

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory - National Institutes of Health (NL-NIH)

Research Benefits
Earth Benefits, Scientific Discovery, Space Exploration

ISS Expedition Duration
March 2015 - September 2015

Expeditions Assigned

Previous Missions
STS-95 STS-107 Russian Foton M3

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Experiment Description

Research Overview

  • Osteocytes are the most abundant cells in bone and reside within the mineralized matrix.
  • Osteocytes are the mechanosensor of bone. They are the cells capable of sensing mechanical forces applied to the skeleton and transform these mechanical forces into biological responses.
  • The molecular (and cellular) mechanisms of mechano-transduction are still poorly understood.
  • The main aim of Osteocytes and mechano-transduction (Osteo-4) is to study gene expression in osteocytes under microgravity conditions.
  • Analysis of gene expression patterns under microgravity  conditions provides insights into mechano-transduction pathways and mineral ion regulation.
  • Results derived from the studies proposed could have significant implications for therapy of bone disorders related to disuse or immobilization.


Osteocytes, the cells deeply embedded in the mineralized matrix, are the mechanosensors of bone. The cellular and molecular mechanisms of mechano-sensing are largely unknown. The osteocyte network is a particular target of research directed at understanding the transmission of the load signal to bone tissue. The main aim of Osteocytes and mechano-transduction (Osteo-4) is to investigate the direct skeletal architectural and hormonal effects of mechanical unloading on gene expression in osteocytes in order to better understand molecular mechanisms of skeletal mechano-sensing.  Specifically, osteocyte SOST/Sclerostin regulation of the Wnt signaling pathway is a benchmark for studying the effect of mechanical unloading on the skeletal system. Furthermore, this novel approach utilizes recent advances in the understanding of the role of FGF23 (fibroblast growth factor) as a novel endocrine regulator of phosphate to benchmark the potential influence of mechanical loading on the ability of osteocytes to maintain the body’s phosphate-calcium homeostasis.

The opportunity to study osteocytes in the International Space Station (ISS) environment (microgravity and minimal fluid shear environment) allows, for the first time, direct analysis of the effects of mechanical forces (or the lack thereof) on osteocyte functions. Osteo-4 utilizes the unique environment of the ISS to study osteocyte responses to microgravity and mechanical unloading conditions. Results from this mission are also used to validate ground-based analogs (NASA-Synthecon Rotating Wall Vessel Bioreactor) to further expand findings derived from this mission.

A novel murine osteocytic cell line that faithfully recapitulates all the hallmarks of bone osteocytes, including expression and secretion of Sclerostin and FGF-23, has been established. These cells are cultured within a 3D scaffold (Alvetex) and exposed to microgravity for short (3 days) and prolonged (7-10 days) periods of time. 
The Osteo-4 system comprises three trays each housing three individual bioreactors. End-points of this mission are analyses of genes expression and morphological changes after short or long periods of exposure to microgravity.

This investigation significantly advances the knowledge of the role of mechanical forces on osteocyte functions and further enhances understanding of these cells. Results derived from the studies proposed here could have significant implications for therapy of bone disorders related to disuse or immobilization (i.e. paralysis).

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Space Applications
Crewmembers lose bone density after extended periods of time in space, and researchers are not exactly sure why. Microgravity and the sensation of weightlessness may contribute to bone density loss, as osteocytes are not subjected to the force of gravity. Osteo-4 studies the function and behavior of isolated bone cells in microgravity to determine how osteocyte function and behavior may contribute to crewmember bone density loss.  

Earth Applications
Patients living with osteopenia, or low bone density, and osteoporosis, a disease that causes reduced bone density, are more likely to suffer broken bones. A better understanding of the mechanisms behind bone loss in astronauts during space flight could also provide insights for bone disorders on Earth.

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Operational Requirements and Protocols

Samples (bioreactors n=3 for each tray) need to be removed from the payload at defined times, disconnected and stored at low temperature (2 bioreactors at -80°C and 1 bioreactor at +4°C). Samples are returned in cold storage.

Payload is transferred powered from vehicle to ISS locker.  According to time of the experiment, individual trays are removed and bioreactors are disconnected and stored at specified temperatures.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Information Pending

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Related Websites

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image NASA Image: ISS043E122576 - ESA astronaut Samantha Cristoforetti working with the Osteo-4 experiment.
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image NASA Image: ISS043E125603 - ESA astronaut Samantha Cristoforetti working with the Osteo-4 experiment.
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image A close-up of mouse osteocytes within the bone. Image courtesy of: Dr. L Bonewald
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image The three colorful bioreactors where mouse bone cells grow within a 3D material for the Osteo-4 investigation aboard the International Space Station. Image courtesy of Divieti Pajevic Laboratory.
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image The Osteo-4 investigation team consists of members from both the Divieti Pajevic Laboratory and CALM Technologies. Image courtesy of: Divieti Pajevic Laboratory
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Sample drawing of Osteocytes and mechano-transduction (Osteo-4) EXPRESS locker. Image courtesy of Paola Divieti Pajevic.

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