Commercial Biomedical Testing Module-3: Assessment of sclerostin antibody as a novel bone forming agent for prevention of spaceflight-induced skeletal fragility in mice (CBTM-3-Sclerostin Antibody) - 03.21.18

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ISS Science for Everyone

Science Objectives for Everyone
Commercial Biomedical Testing Module-3: Assessment of sclerostin antibody as a novel bone forming agent for prevention of spaceflight-induced skeletal fragility in mice (CBTM-3-Sclerostin Antibody) is one in a series of investigations designed to determine if administering an experimental agent preflight reduces the loss of bone associated with space flight. Humans and animals have been observed to lose bone mass during the reduced gravity of space flight. The sclerostin antibody is designed to inhibit the action of "sclerostin", a protein that is a key negative regulator of bone formation, bone mass and bone strength.
Science Results for Everyone
Nothing modest about these mice. This investigation using mice aboard the space station indicated increased blood flow to the brain, which is likely a factor in astronaut vision impairment and problems regulating standing blood pressure. Other data suggested mice are not ideal test subjects for studying a possible connection between blood supply and bone loss. But scientists used tissues from these mice to identify microgravity effects on a variety of systems including arteries in the brain, intestines, and muscles; muscle fibers; skin structure; lung tissue; spinal discs; the immune system; and microbes in the digestive system.

The following content was provided by Chris Paszty, Ph.D., Louis S. Stodieck, Ph.D., Hua Zhu (David) Ke, M.D., Martyn Robinson, PhD., Virginia L. Ferguson, Ph.D., Mary L. Bouxsein, Ph.D., Ted A. Bateman, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details


Principal Investigator(s)
Chris Paszty, Ph.D., Amgen, Inc., Thousand Oaks, CA, United States
Louis S. Stodieck, Ph.D., University of Colorado, BioServe Space Technologies, Boulder, CO, United States
Hua Zhu (David) Ke, M.D., Thousand Oaks, CA, United States
Martyn Robinson, PhD., UCB in Brussels, Brussels, Belgium
Virginia L. Ferguson, Ph.D., University of Colorado, Boulder, CO, United States
Mary L. Bouxsein, Ph.D., Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States
Ted A. Bateman, Ph.D., University of North Carolina, Chapel Hill, NC, United States

Information Pending

Amgen Research, Thousand Oaks, CA, United States
BioServe Space Technologies, Boulder, CO, United States
NASA Ames Research Center, Moffett Field, CA, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Information Pending

ISS Expedition Duration
March 2011 - September 2011

Expeditions Assigned

Previous Missions
A similar investigation, CBTM, flew round trip to the ISS on STS-108 during ISS Expedition 4. CBTM-2 flew round trip to the ISS on STS-118 during ISS Expedition 15. AEMs have flown on numerous space shuttle missions over the years.

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Experiment Description

Research Overview

  • The loss of bone mass during space flight remains a significant problem for human space missions, especially long-duration space flights. Varieties of countermeasures have been tried, mostly based on exercise, but have not proven to be totally effective in reducing bone loss.

  • Commercial Biomedical Testing Module-3: Assessment of sclerostin antibody as a novel bone forming agent for prevention of spaceflight-induced skeletal fragility in mice (CBTM-3-Sclerostin Antibody) is an investigation focusing on a novel experimental agent. The agent is an antibody against the protein, sclerostin, a protein that is known to inhibit bone formation. If the agent is effective in reducing or preventing bone loss in mice during the flight, then it will demonstrate the potential for pharmacologic inhibition of sclerostin to be further tested for use in astronauts and in patients under disuse conditions. A different sclerostin antibody than the one being used for this STS-135 mouse study is currently in clinical trials as a collaboration between Amgen Inc. and UCB.


Commercial Biomedical Testing Module-3: Assessment of sclerostin antibody as a novel bone forming agent for prevention of spaceflight-induced skeletal fragility in mice (CBTM-3-Sclerostin Antibody) is part of a suite of investigations studying the ability of novel experimental agents to prevent disuse induced bone loss, and extend current knowledge about the effects of microgravity on the musculoskeletal system and the ability of a ground-based analog system (rodent hind limb suspension) to reproduce those effects in mice. The ultimate objective is to mitigate the risk for space-induced skeletal fragility associated with missions to low Earth orbit, and exploration destinations. If the sclerostin antibody proves successful in reducing space flight induced bone mass loss in mice, then it will demonstrate the potential for pharmacologic inhibition of sclerostin to be used in astronauts. Beyond the perils of microgravity, the findings may also provide novel insight into prevention and treatment of the skeletal fragility that can result from “skeletal disuse” in such conditions as immobilization, stroke, cerebral palsy, muscular dystrophy, spinal cord injury, and reduced physical activity. Eight to ten mice are flown in each of three Animal Enclosure Modules (AEMs) ( located on the space shuttle middeck. Half of the mice are given a preflight injection of a novel experimental bone forming agent, an antibody designed to inhibit the activity of the protein “sclerostin”. The remaining mice receive a placebo. Following the flight, a team of scientists, are studying various aspects of the structure, composition, strength, and cell and molecular nature of the bones from the flight and ground-based control mice. Bones from mice receiving the bone forming agent are compared to those receiving the placebo and are also compared to a ground control group, i.e., mice that were housed in AEM's on the ground during the flight.

This research is also expected to contribute data to the current body of research on microgravity effects on the skeletal, cardiovascular, and immune systems, liver and kidney function as well as other physiological systems through a tissue sharing program. Every effort will be made to harvest as many different samples and types of tissue from the mice as possible for other mission specific biomedical research. Positive results from this research may advance our understanding of mechanistic changes that occur in various physiological systems after exposure to microgravity and support overall efforts to reduce health risks to crewmembers. The investigations resulting from the CBTM-3 tissue sharing program are as follows:

  • Brain
    • Alan R. Hargens, University of California San Diego, La Jolla CA
    • Michael Pecaut, Ph.D, Loma Linda University, Loma Linda, CA
    • Gregory A. Nelson, Ph.D. , Loma Linda University, Loma Linda, CA
    • Xiao Wen Mao, M.D., Loma Linda University, Loma Linda, CA
  • Eyes
    • Susana B. Zanello, Ph.D., Universities Space Research Association, Houston, TX
    • Xiao Wen Mao, M.D., Loma Linda University, Loma Linda, CA
  • Lung
    • Roberto Garofalo, M.D., University of Texas Medical Branch, Galveston, TX
    • Xiao Wen Mao, M.D., Loma Linda University, Loma Linda, CA
  • Kidneys and Small Intestine
    • Moshe Levi, University of Colorado, Denver, CO
  • Liver
    • Karen Jonscher, Ph.D.,  University of Colorado, Denver CO
    • Michael Pecaut, Ph.D, Loma Linda University, Loma Linda, CA
    • Jian Tian, Ph.D., Loma Linda University, Loma Linda, CA
    • Scott  M. Smith, Ph.D., Johnson Space Center, Houston, TX
    • Virginia E. Wotring, Ph.D., Universities Space Research Association, Houston, TX
  • Metatarsals
    • Eduardo Almeida, Ph.D.,  Ames Research Center, Moffett Field, CA
  • Distal Tibia and Tarsus
    • Hiroki Yokota, Ph.D., Indiana University-Purdue University Indianapolis, Indianapolis, IN
  • Thymus
    • Millie Hughes-Fulford, Ph.D.,  University of California, San Francisco, San Francisco, CA
    • Daila S. Gridley, Loma Linda University, Loma Linda, CA
  • Spleen
    • Millie Hughes-Fulford, Ph.D.,  University of California, San Francisco, San Francisco, CA
    • Michael Pecaut, Ph.D, Loma Linda University, Loma Linda, CA
  • Extensor digitorum longus, transversus abdominis and masseter muscle
    • Elisabeth R. Barton, Ph.D., University of Pennsylvania, Philadelphia, PA
  • Temporal Bones
    • Richard D. Boyle, Ph.D., Universities Space Research Association, Moffett Field, CA
    • Larry F. Hoffman, Ph.D.,  University of California Los Angeles, Los Angeles, CA
    • Shin-ichi Usami, M.D., Shinshu University, Matsumoto, Japan
  • Cerebral Artery, Mesenteric Vein, Heart, Soleus
    • Michael D. Delp, Ph.D.,  University of Florida, Gainesville, FL
  • Adrenals
  •     Michael Pecaut, Ph.D, Loma Linda University, Loma Linda, CA
  • Femoral Heads, Quadriceps and Skin
    • David Fitzgerald, Ph.D.,  Oregon Health and Science University, Portland, OR
  • Tail
    • Alan R. Hargens, University of California San Diego, La Jolla CA
  • Heart, Soleus, Extensor digitoum longus and transversus abdominis
    • Brooke C. Harrison, Ph.D., University of Colorado, Boulder, CO
  • Biceps brachii and Triceps brachi
    • Akihiko Ishihara, Ph.D.,  Kyoto University, Kyoto, Japan
  • Skin
    • Xiao Wen Mao, M.D., Loma Linda University, Loma Linda, CA
    • Masahiro Terada, Japan Aerospace Exploration Agency, Tsukuba, Japan
  • Uterine horn, ovaries, stomach
    • Joseph S. Tash, Ph.D., University of Kansas Medical Center, Kansas City, KS
  • Distal Colon and Fecal Pellets
    • Scott  M. Smith, Ph.D., Johnson Space Center, Houston, TX
  • Salivary glands and 1/4 the left ventricle
    • Maija Mednieks, Ph.D., University of Connecticut Health Center, Farmington, CT
  • Humerus, rotator cuff, scapula units  and Achilles tendon calcaneus units
    • Stavros Thomopoulos, Ph.D., Washington University, St. Louis, MO
  • Meniscus
    • Jeffrey Willey, Ph.D.,  Wake Forest School of Medicine, Winston-Salem, NC

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Space Applications
If the novel bone forming agent proves successful in mitigating bone mass loss in-flight, this would demonstrate the potential application of pharmacologic sclerostin inhibition as a countermeasure for use in long-duration human space flight missions.

Earth Applications
If the sclerostin antibody proves successful in reducing space flight induced bone mass loss, the results may point towards possible prevention and treatment of the bone loss that can result from “skeletal disuse” in such conditions as immobilization, stroke, cerebral palsy, muscular dystrophy, spinal cord injury, and reduced physical activity.

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Operational Requirements and Protocols

AEM's with eight to ten mice each are requested for a late load (Launch minus 72 to 24 hours) and to be removed postflight within four hours of landing. During flight the crew is requested to conduct a daily health check of the mice, i.e., a visual observation through the Lexan lid of the AEMs. Unusual appearances of the mice are to be reported as soon as possible.

For this study nine week old female C57BL/6 mice are launched on the space shuttle. Flight mice are treated once with a placebo vehicle or the bone forming agent approximately 24 hours before launch. Ground control mice are treated in the same manner but with a 48 hour offset. Ground control mice are housed under the same environmental conditions (temperature, light/dark cycle, humidity, oxygen levels and carbon dioxide levels) as the flight mice. All mice receive the same full access to food and water. Upon return to Earth, the AEMs are returned to the research team for analysis. Body weight is also measured preflight and postflight. Statistical comparisons will be made between the treated and control mice.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Biceps brachii and Triceps brachi:
The effects of 13-day exposure to microgravity on the muscle fiber properties of the mouse triceps brachii (large muscle on the back of the upper arm) is investigated. Results show that short-term exposure causes a decrease in oxidative capacity, but did not affect the body weight, muscle weight, or fiber cross-sectional area, in the triceps brachii of mice. The triceps brachii is a fast-twitch muscle without much activity against gravity, resulting in relative resistance to microgravity conditions, and thus a lack of fiber atrophy. By contrast, the slow-twitch muscles and high-oxidative fibers are distributed exclusively in the hind limbs, and weightlessness has a greater effect on these muscles and fibers in rodents because their function and metabolism depend on gravity. Rodent hind-limb muscles, especially the slow soleus, develop atrophy of all types of fibers and type shifting of fibers from slow twitch (type I) to fast twitch (type II) after exposure to microgravity. Microgravity results correspond well with previous findings obtained in ground studies, demonstrating atrophy to a greater extent in slow muscles and high-oxidative fibers than in fast muscles and low-oxidative fibers. The mechanisms underlying decreased oxidative capacity in the triceps brachii muscle under microgravity conditions are not defined clearly, but may be associated with the reduced oxidative enzyme activity of spinal motor nerves controlling that muscle. If decreased muscle oxidative capacity in the upper limbs of humans is induced by exposure to microgravity, as it is in the forelimb muscles of the test rodents, then chronic endurance exercise of skeletal muscles in the upper limbs would be needed to maintain muscle oxidative capacity in space (Akihiko et al. 2015)
Cerebral Artery, Mesenteric Vein, Heart, Soleus:
Data from 13 days of space flight reveal that arterial contraction is lessen in brain arteries of mice, passive pressure-diameter response indicated greater ability for vascular expansion and contraction, and mechanical testing revealed that the arteries from space flight animals had lower elasticity and stiffness. Gross structural measurements show that maximum brain arterial diameter is greater in space flight mice, while average wall thickness is similar to ground control mice. These results demonstrate that space flight alters vasoconstrictor, mechanical and gross structural properties, and resistance of cerebral arteries. Although higher carbon dioxide (CO2) concentration typical in the closed spacecraft environment may contribute to alterations in the properties of cerebral arteries, high CO2 levels alone cannot fully account for the changes seen. These alterations imply that blood flow to the brain may be increased during space flight. If similar changes occur in humans during space flight, increase in brain blood flow could elevate intracranial pressure and possibly contribute to the visual impairment reported in astronauts (Taylor et al. 2013).
The theory that arteries and veins supplying the intestine suffer diminished constricting ability after spaceflight is tested. Results demonstrate that spaceflight diminishes the magnitude and rapidity of mesenteric artery vasoconstriction in mice. These changes in arterial vasoconstriction occurred in the absence of any gross structural changes in artery medial wall thickness or diameter, or through any alterations in the passive mechanical properties of the vessels. This dysfunction persists 1 day post spaceflight, but returns 5 days later. The results suggest that the decrease in mesenteric arterial vasoconstriction could cause astronauts not able to maintain Pulmonary Vascular Resistance (PVR) and mean arterial blood pressure (MAP) during upright posture shortly upon returning to Earth. Furthermore, the impairment of arterial and venous constriction could diminish the ability to centrally mobilize blood volume to maintain venous filling pressure, and pump the normal amount of blood from the heart to the body during standing up and exercising stress (Behnke et al. 2013).
Researchers also investigate the influence of space flight on the constriction of mouse muscle arteries either in response to a stimulus (vasoconstriction) or under their own power (myogenic contraction) and to determine the impacts on bone and muscle mass loss. Total body mass and muscle mass tend to be lower in space flight mice. Space flight was found to decrease vasoconstrictor responses but did not affect the myogenic responsiveness. The thickness of the vessel walls is similar between the two groups. The lack of change in vessel wall thickness suggests that the blood volume redistribution is insignificant in mice during space flight and likely reflects that blood flow to the portion of muscle being tested is normal. This is an important shortcoming and demonstrates that the mouse may not be an ideal animal model to study this phenomenon. If applicable to the human condition, these results suggest that microgravity-induced changes in the vasoconstrictor characteristics of skeletal muscle resistance arteries could compromise the ability to raise peripheral vascular resistance in order to regulate arterial blood pressure when standing (Stabley et al. 2012).
Distal Colon and Fecal Pellets:
Not much research has been done to understand the effect of low dose radiation and microgravity inside the colon and intestinal lining. The aim of this study is to see how high and low linear energy transfer (LET) radiation, microgravity, and elevated dietary iron affect microbes in the colon and colon function since astronauts’ intestinal health may be impacted by these factors. It is found in mice that low LET radiation, IRON, and spaceflight did not significantly affect the diversity or richness, or elevate harmful bacteria in the gut, and no differences in colon epithelial injury or inflammation is observed. Although there are little differences, distinct shifts in bacterial populations are noted in animals exposed to microgravity following elevated dietary iron consumption, radiation exposure, and spaceflight. These observations suggest some unique alterations to the microbiota when exposed to a space environment compared to other disruptions to normal intestinal function such as gastrointestinal disease. These findings could also provide insight for airline crews, radiation workers, and patients receiving heavy-ion cancer therapy. Microbiota and mucosal characterization in mice models is a first step in understanding the impact of the space environment on human intestinal health (Lauren et al. 2015).
Extensor digitorum longus, transversus abdominis and masseter muscle:
The body’s muscles need to do work to maintain their mass and strength. Researchers compare the responses of masseter (MA) muscles, use for chewing, in mice with limb muscles because these muscles operate under different loading conditions even when subjected to the same microgravity environment. It is found that limb muscles underwent atrophy in response to microgravity, evident by the loss of mass, alterations in mechanical loading signaling pathways, and in the balance between pro- and antigrowth gene expression. To determine if loss of work for masticatory muscles would also result in fiber atrophy, mice were subjected to a liquid diet. After 2 weeks on a liquid diet, the superficial MA fiber size decreased significantly and fiber size was reduced. These results support that doing physical work is a significant factor in determining muscle fiber size independent of the origin of the muscles. These findings indicate that continued mechanical loading (work) of skeletal muscle in a weightlessness environment can reduce atrophy but still may not be sufficient to protect against loss of power (Anastassios et al. 2015).
As use of the International Space Station (ISS) is increased, and with the rise of commercial spaceflight and tourism, the effects of microgravity on human health must be carefully investigated. Spaceflight affects many organs in the body including the liver, and whether the liver is vulnerable to injury or dysfunction resulting from spaceflight remains an open question. The goal of this study was to comprehensively characterize liver molecular and functional changes in mice flown aboard the orbiter Atlantis - the final Shuttle mission. Scientists found that the space mice lose twice as much weight (12% of body weight as compared with 6% lost by ground-control mice) during the mission but redistribute fats, or lipids molecules, particularly to the liver. Intriguingly, flown mice lose retinol (a vitamin essential for healthy vision, bone development, reproduction, skin and mucous membranes) from lipid droplets, have increased bile acids, and show early signs of liver injury. Chronic hyperlipidemia (excess fat storage) and oxidative stress, a well-known complication of exposure to microgravity, cause activation of hematopoietic stem cells (HSCs) or hemocytoblasts, increased loss of HSC lipid droplets and their retinoid stores, accompanied by progressive scarring of the liver. Some of these changes may represent early signs of Non-alcoholic fatty liver disease (NAFLD), the build up of extra fat in liver cells that is not caused by alcohol, which involves a spectrum of liver abnormalities, ranging from hepatic steatosis, or fat droplet accumulation, to nonalcoholic steatohepatitis (NASH), causing inflammation and fibrosis and resulting in irreversible tissue damage in many cases. Although the 13-day flight duration is too short for outright fibrosis to develop, the retinol loss plus changes in the internal supporting structures of liver cells raise the concern that longer duration exposure to the space environment may increase risk of liver damage. Further study in this area is needed and analysis of tissues harvested in space from mice flown aboard the ISS for many months may help determine whether long-term spaceflight might lead to hepatic injury and whether damage can be prevented (Jonscher et al. 2016).
This research evaluates changes in lung health due to spaceflight stressors that include radiation above levels found on Earth. Space-flown mice lung tissue is collected to evaluate the expression of genes related to lung tissue adhesion and stem cell signaling. Pathway analysis is also performed. The results demonstrate that spaceflight-related stress had a significant impact on lung integrity, indicative of tissue injury and structural changes. Among the number of genes affected, the greatest effect is seen on osteonectin, the gene for making protein that has anti-adhesive properties, inhibits cell proliferation, and regulates activity of certain growth factors (Gridley et al. 2015). Skin: The skin is a uniquely vulnerable organ because it is always exposed to the external environment, and the probable occurrence of skin diseases ranks high for space flight and has long been a concern. Skin has many important barrier functions, but the two that are critical for survival are the barrier to the movement of water and electrolytes and the barrier against invasive and toxic microorganisms. Expected skin disorders from spaceflight include contact dermatitis due to altered cell-mediated immunity, risk of cancer from radiation exposure, impaired wound healing, and loss of elasticity. Analysis of mouse skin after space flight indicates oxidative stress and changes to the extracellular matrix (ECM) - a collection of extracellular molecules secreted by cells that provides structural and biochemical support to tissues. Collectively, data show that space flight condition leads to a shift in homeostasis as the consequence of changes in the cellular antioxidant defense system, increases in production of reactive oxygen species (ROS), which, in turn are accompanied by increased level of oxidative stress and tissue changes through altered expression of genes involved in the accumulation and degradation of ECM components. These results infer that astronauts may be at increased risk for skin diseases. This study also show that space flight condition alters several aspects of skin metabolic pathways that lead to skin injury (Mao et al. 2014).
Prolonged spaceflight is thought to adversely affect the human spine because of reports that disc herniation risk increases post-spaceflight, and the risk appears highest during the first post-spaceflight year and gradually subsides thereafter. However, research on mice reveals no evidence of disc recovery over the first 7-day post-spaceflight period. By contrast, the data trends suggest that the disc properties continued to worsen relative to ground based control mice. This finding supports other studies that demonstrate degenerative effects of prolonged microgravity on spinal discs. Additionally, recovery is not seen over a week post spaceflight, suggesting matrix or cell damage as opposed to passive, transient fluid shifts. It could also be that one week is not long enough for recovery mechanisms to take effect. Further research is needed regarding the state of the post-spaceflight intervertebral disc and whether or not microgravity is posing permanent damage on the disc (Bailey et al. 2012).
Alterations in immune function have been documented during or post-spaceflight and in ground based simulated microgravity studies. This research completes a broader spectrum analysis of changes in mouse white blood cells after 13 days of orbital flight. Evidence shows that spaceflight does impact defense cell activity and cause global reduction in response to a variety of antigens during and after spaceflight. The data from this study shed additional light towards molecular mechanisms involved in immune changes induced by spaceflight that could alter activation of innate (general non-specific) and adaptive (highly specific to the particular pathogen) immunity. Future analysis should continue to examine both innate and adaptive immune responses to determine if changes may also impact responses during active flight (Shen-An et al. 2015).
Temporal Bones:
Bone loss is one of the most serious and difficult to control health dangers of human spaceflight. It is known, that changes in bone from living in space are not the same throughout the skeleton. For instance, while bone mineral density (BMD) decreases in the lower extremities (weight bearing long bones), it increases in the skull. Spaceflight increases skull BMD in humans, rats, and mice, and it has been suggested that fluid shifts to the head from the lack of gravity could be the cause. It is thought that if cephalic fluid shifts were increasing bone building activity in the skull, the same effect would be seen in other non-weight bearing bones in the head - mainly the jaw bone. However, spaceflight led to opposite changes in the mandibular bone properties, shown by decreased bone volume compared to ground controls. Results from the study of mandibles combined with those of the skull from mice indicate that that non-weight bearing bones are altered in a weightless environment as well, and other factors associated with spaceflight, such as elevated CO2 levels, vascular adaptations, elevated intracranial pressure, may also be important factors which affect the changes of non-weight bearing bones in the head (Ghosh et al. 2016).

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Results Publications

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Ground Based Results Publications

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ISS Patents

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Related Publications

    Spatz JM, Ellman R, Cloutier AM, Louis L, van Vliet M, Suva LJ, Dwyer D, Stolina M, Ke HZ, Bouxsein ML.  Sclerostin antibody inhibits skeletal deterioration due to reduced mechanical loading. Journal of Bone and Mineral Research. 2013 April; 28(4): 865-874. DOI: 10.1002/jbmr.1807. PMID: 23109229.

    O-Brien CA, Plotkin LI, Galli C, Goellner JJ, Gortazar AR, Allen MR, Robling AG, Bouxsein ML, Schipani E, Turner CH, Jilka RL, Weinstein RS, Manolagas SC, Bellido T.  Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PLOS ONE. 2008; 3(8): 2942. DOI: 10.1371/journal.pone.0002942. PMID: 18698360.

    Wagner EB, Granzella NP, Saito H, Newman DJ, Young LR, Bouxsein ML.  Partial weight suspension: a novel murine model for investigating adaptation to reduced musculoskeletal loading. Journal of Applied Physiology. 2010 August; 109(2): 350-357. DOI: 10.1152/japplphysiol.00014.2009. PMID: 20522735.

    Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, Li Y, Feng G, Gao X, He L.  Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. Journal of Bone and Mineral Research. 2009 Oct; 24(10): 1651-1661. DOI: 10.1359/jbmr.090411. PMID: 19419300.

    Devlin MJ, Cloutier AM, Thomas NA, Panus DA, Lotinun S, Pinz I, Baron R, Rosen CJ, Bouxsein ML.  Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. Journal of Bone and Mineral Research. 2010; 25(9): 2078-88. DOI: 10.1002/jbmr.82. PMID: 20229598.

    Ferguson VL, Ayers RA, Bateman TA, Simske SJ.  Bone development and age-related bone loss in male C57BL/6J mice. Bone. 2003; 33(3): 387-398. DOI: 10.1016/S8756-3282(03)00199-6. PMID: 13678781.

    Liu X, Bruxvoort KJ, Zylstra CR, Liu J, Cichowski R, Faugere M, Bouxsein ML, Wan C, Williams BO, Clemens TL.  Lifelong accumulation of bone in mice lacking Pten in osteoblasts. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(7): 2259-64.

    Lang TF, LeBlanc AD, Evans HJ, Lu Y, Genant HK, Yu A.  Cortical and Trabecular Bone Mineral Loss from the Spine and Hip in Long-duration Spaceflight. Journal of Bone and Mineral Research. 2004; 19(6): 1006-1012. DOI: 10.1359/JBMR.040307.

    Spatz JM, Fields EE, Yu EW, Pajevic PD, Bouxsein ML, Sibonga JD, Zwart SR, Smith SM.  Serum sclerostin increases in healthy adult men during bed rest. Journal of Clinical Endocrinology and Metabolism. 2012 September; 97(9): E1736-1740. DOI: 10.1210/jc.2012-1579. PMID: 22767636.

    Li X.  Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats. Journal of Bone and Mineral Research. 2010; 25(12): 2647-2656. DOI: 10.1002/jbmr.182. PMID: 20641040.

    Ellman R, Spatz JM, Cloutier AM, Palme R, Christiansen BA, Bouxsein ML.  Partial reductions in mechanical loading yield proportional changes in bone density, bone architecture, and muscle mass. Journal of Bone and Mineral Research. 2013 April; 28(4): 875-885. DOI: 10.1002/jbmr.1814. PMID: 23165526.

    Fajardo RJ, Manoharan RK, Pearsall RS, Davies MV, Marvell T, Monnell TE, Ucran JA, Pearsall AE, Khanzode D, Kumar R, Underwood KW, Roberts B, Seehra J, Bouxsein ML.  Treatment with a soluble receptor for activin improves bone mass and structure in the axial and apendicular skeleton of female cynomolgus macaques (Macaca fascicularis). Bone. 2010; 46(1): 64-71. DOI: 10.1016/j.bone.2009.09.018. PMID: 19781677.

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Related Websites
Space Biosciences Division

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image NASA Image: S118E09327 - STS-118 Mission Specialist Tracy Caldwell and Pilot Charles Hobaugh observing the Animal Enclosure Modules (AEMs) in the Middeck of the Space Shuttle Endeavour.
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image Animal Enclosure Modules (AEMs) from NASA Ames Research Center. Image courtesy of NASA.
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