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Cellular Mechanisms Underlying Bone-Forming Cell Proliferative Response to HypergravityLife on Earth has evolved under the continuous influence of gravity (1-g). As humans explore and develop space, however, we must learn to adapt to an environment with little or no gravity. Studies indicate that lack of weightbearing for vertebrates occurring with immobilization, paralysis, or in a microgravity environment may cause muscle and bone atrophy through cellular and subcellular level mechanisms. We hypothesize that gravity is needed for the efficient transduction of cell growth and survival signals from the extra-cellular matrix (ECM) (consisting of molecules such as collagen, fibronectin, and laminin) in mechanosensitive tissues. We test for the presence of gravity-sensitive pathways in bone-forming cells (osteoblasts) using hypergravity applied by a cell culture centrifuge. Stimulation of 50 times gravity (50-g) increased proliferation in primary rat osteoblasts for cells grown on collagen Type I and fibronectin, but not on laminin or uncoated surfaces. Survival was also enhanced during hypergravity stimulation by the presence of ECM. Bromodeoxyuridine incorporation in proliferating cells showed an increase in the number of actively dividing cells from about 60% at 1-g to over 90% at 25-g. Reverse transcription-polymerase chain reaction was used to test for all possible integrins. Our combined results indicate that beta1 and/or beta3 integrin subunits may be involved. These data indicate that gravity mechanostimulation of osteoblast proliferation involves specific matrix-integrin signalling pathways which are sensitive to g-level. Further research to define the mechanisms involved will provide direction so that we may better adapt and counteract bone atrophy caused by the lack of weightbearing.
Document ID
20040081243
Acquisition Source
Ames Research Center
Document Type
Conference Paper
Authors
Vercoutere, W.
(NASA Ames Research Center Moffett Field, CA, United States)
Parra, M.
(NASA Ames Research Center Moffett Field, CA, United States)
DaCosta, M.
(NASA Ames Research Center Moffett Field, CA, United States)
Wing, A.
(NASA Ames Research Center Moffett Field, CA, United States)
Roden, C.
(NASA Ames Research Center Moffett Field, CA, United States)
Damsky, C.
(California Univ. San Francisco, CA, United States)
Holton, E.
(NASA Ames Research Center Moffett Field, CA, United States)
Searby, N.
(NASA Ames Research Center Moffett Field, CA, United States)
Globus, R.
(NASA Ames Research Center Moffett Field, CA, United States)
Almeida, E.
(NASA Ames Research Center Moffett Field, CA, United States)
Date Acquired
August 21, 2013
Publication Date
March 28, 2004
Subject Category
Life Sciences (General)
Meeting Information
Meeting: Astrobiology Conference
Country: Unknown
Start Date: March 28, 2004
End Date: April 1, 2004
Funding Number(s)
CONTRACT_GRANT: NASA-00-OBPR-01-066
Distribution Limits
Public
Copyright
Work of the US Gov. Public Use Permitted.

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