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Regulation of Osteoblast Survival by the Extracellular Matrix and GravitySpaceflight adversely affects the skeleton, posing a substantial risk to astronaut's health during long duration missions. The reduced bone mass observed in growing animals following spaceflight is due at least in part to inadequate bone formation by osteoblasts. Thus, it is of central importance to identify basic cellular mechanisms underlying normal bone formation. The fundamental ideas underlying our research are that interactions between extracellular matrix proteins, integrin adhesion receptors, cytoplasmic signaling and cytoskeletal proteins are key ingredients for the proper functioning of osteoblasts, and that gravity impacts these interactions. As an in vitro model system we used primary fetal rat calvarial cells which faithfully recapitulate osteoblast differentiation characteristically observed in vivo. We showed that specific integrin receptors ((alpha)3(beta)1), ((alpha)5(beta)1), ((alpha)8(betal)1) and extracellular matrix proteins (fibronectin, laminin) were needed for the differentiation of immature osteoblasts. In the course of maturation, cultured osteoblasts switched from depending on fibronectin and laminin for differentiation to depending on these proteins for their very survival. Furthermore, we found that manipulating the gravity vector using ground-based models resulted in activation of key intracellular survival signals generated by integrin/extracellular matrix interactions. We are currently testing the in vivo relevance of some of these observations using targeted transgenic technology. In conclusion, mechanical factors including gravity may participate in regulating survival via cellular interactions with the extracellular matrix. This leads us to speculate that microgravity adversely affects the survival of osteoblasts and contributes to spaceflight-induced osteoporosis.
Document ID
20010076245
Acquisition Source
Ames Research Center
Document Type
Conference Paper
Authors
Globus. Ruth K.
Almeida, Eduardo A. C.
Searby, Nancy D.
Bowley, Susan M.
Date Acquired
August 20, 2013
Publication Date
January 13, 2000
Subject Category
Life Sciences (General)
Meeting Information
Meeting: 2001 NASA Cell Science Conference
Location: Houston, TX
Country: United States
Start Date: March 6, 2001
End Date: March 8, 2001
Funding Number(s)
CONTRACT_GRANT: NAGW-4625
CONTRACT_GRANT: 99-HEDS-02-062
Distribution Limits
Public
Copyright
Work of the US Gov. Public Use Permitted.

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