ASGSB 2003 Annual Meeting Abstracts


[52]

MOLECULAR THERAPIES FOR DISUSE OSTEOPOROSIS.  T.A. Bateman. Bioengineering Department, Clemson University, Clemson, SC.

   Microgravity causes changes in physiological systems that are both detrimental to human health and beneficial for biomedical research.  Two of the most pronounced changes occur in muscle and skeletal tissue, with both experiencing a profound and rapid wasting.  Finding a countermeasure to the bone loss and muscle atrophy associated with weightlessness is necessary before long-duration human space exploration can be possible.  However, these physiological changes can also be exploited as a biomedical model for osteoporosis and sarcopenia, offering an extreme environment in which therapeutics can be tested and mechanisms examined.  Using space as a biomedical test-bed is what was accomplished with the Commercial Biomedical Testing Module (CBTM) payload on STS-108.  The biotechnology company Amgen examined the ability of osteoprotegerin (OPG) to mitigate the osteoporosis caused by microgravity.  OPG is a protein that has been demonstrated to be critical to the differentiation and activation of osteoclastic bone resorption.  Amgen is developing OPG as a treatment for osteoporosis and the bone loss associated with metastatic bone cancer.  Mice experienced a decline in bone strength (15-20% relative to ground controls) over the 12-day flight that was greater than that of ground-based disuse models.  The mechanical testing data was complimented by serum, mRNA and histological analyses that indicated a decline in bone formation and an increase in bone resorption in addition to an inhibition of mineralization.  OPG mitigated the decline in mechanical strength by preventing the increase in resorption and maintaining mineralization.  In addition to this detailed analysis of skeletal properties, a secondary analysis of calf muscles from placebo treated specimens was performed to collect baseline data to validate space-flow mice as an appropriate model for sarcopenia.  Spaceflight caused a 15-30% decline in muscle fiber diameter size compared to appropriate ground controls. 

(Supported by NASA/SC EPSCoR)

 

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