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EXPERIMENT INFORMATION

Optimization of a Biomechanical Countermeasure for Disuse Osteoporosis (NAG53950)
Principal Investigator
Research Area:
Bone and calcium physiology
Species Studied
Scientific Name: Rattus norvegicus Species: Rat Strain: Sprague-Dawley

Description
OBJECTIVES:
The current tenet of mechanically related bone adaptation suggests that mechanical signals must be large in magnitude to stimulate bone formation. In contrast to this bigger is better perspective, recent studies have demonstrated the strong anabolic potential of extremely low magnitude - but high frequency - mechanical signals. Considering the osteogenic character of these high frequency mechanical stimuli, we hypothesize that introducing these signals will serve as an effective countermeasure for the bone loss which parallels disuse. Importantly, these low level signals may play a critical role in defining and maintaining normal bone mass and morphology, as they persist over long durations, including passive actions such as standing, and therefore represent a dominant component of bone's functional strain history. Not surprisingly, therefore, conditions such as microgravity (or a model of this pathology such as rat-tail suspension) may abolish this key regulatory stimulus, and thus permit resorptive activity. In an effort to reintroduce these low-level mechanical stimuli, we have devised a prototype, categorized as "non-significant risk" by the FDA, which can increase bone formation by inducing extremely low level mechanical stimuli into the lower appendicular and axial skeleton. Importantly, this unique biomechanical intervention affords the ability to examine the molecular basis of an osteogenic signal, thus identifying novel targets for drug development. Osteoclast differentiation factor (ODF) is a cytokine involved the recruitment and activity of osteoclasts and in vitro studies have linked its upregulation to the absence of mechanical strain. Here, we first examined the osteogenic efficacy of low-level high frequency mechanical stimuli and their ability to reverse the bone loss which arises under microgravity. We then hypothesized that the expression of ODF would be inversely related to altered tissue level bone formation rates.


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Publications
Judex S, Donahue LR, Rubin C. Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. FASEB J 2002 Aug; 16(10):1280-2, 2002.[pubmed.gov]

Rubin C, Xu G, Judex S. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli. FASEB J. 2001 Oct;15(12):2225-9.[pubmed.gov]

Keywords
Adaptation, physiological
Bone and bones
Genetic predisposition to disease
Hindlimb suspension
Models, genetic
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Data Information
Data Availability
Archive is complete. All data sets are on the Web site.
Data Sets + View data.

Parameters
Bone formation rate
Bone tissue response
Bone volume
Glyceraldehyde 3 phosphate dehydrogenase GAPDH
Labeled surface of bone
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Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
BRC 01/01/2003 12/31/2005 1095 days

Additional Information
Managing NASA Center
Johnson Space Center (JSC)
Responsible NASA Representative
Johnson Space Center LSDA Office
Project Manager: Pamela A. Bieri
Institutional Support
National Aeronautics and Space Administration (NASA)
Proposal Source
NAG-5-3950