| Bone cell survival in microgravity: evidence that modeled microgravity increases osteoblast sensitivity to apoptogens. | |
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MedLine Citation:
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PMID: 15644346 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Studies were performed to evaluate the effects of modeled microgravity on the induction of osteoblast apoptosis. MC3T3-E1 osteoblast-like cells were cultured in alginate carriers in the NASA-approved high aspect ratio vessel (HARV). This system subjects the cells to a time-averaged gravitational field (vector-averaged gravity) to simulate low gravity conditions. Cells were cultured in the HARV for five days, and then examined for apoptosis. In simulated microgravity, the cells remained vital, although analysis of expressed genes indicated that there was loss of the mature osteoblast phenotype. Additionally, we noted that there was a loss of the mitochondrial membrane potential, a low level of the antiapoptotic protein Bcl-2, as well as Akt protein, and the redox status of the cells was disturbed. All of these parameters indicated that vector-averaged gravity disrupts mitochondrial function, thereby sensitizing osteoblasts to apoptosis. We then used a challenge assay to evaluate the apoptotic sensitivity of the cells subjected to vector-averaged gravity. When challenged with staurosporine, cells subjected to vector-averaged gravity evidenced elevated levels of cell death relative to control cell populations. Another objective of the study was to improve upon conventional carriers by using alginate encapsulation to support cells in the HARV. We have demonstrated that the alginate carrier system affords a more robust system than surface-seeded carriers. This new system has the advantage of shielding cells from mechanical damage and fluid shear stresses on cells in the HARV, permitting carefully controlled studies of the effects of vector-averaged gravity. |
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Authors:
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M A Bucaro; J Fertala; C S Adams; M Steinbeck; P Ayyaswamy; K Mukundakrishnan; I M Shapiro; M V Risbud |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Annals of the New York Academy of Sciences Volume: 1027 ISSN: 0077-8923 ISO Abbreviation: Ann. N. Y. Acad. Sci. Publication Date: 2004 Nov |
Date Detail:
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Created Date: 2005-01-12 Completed Date: 2005-02-18 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7506858 Medline TA: Ann N Y Acad Sci Country: United States |
Other Details:
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Languages: eng Pagination: 64-73 Citation Subset: IM; S |
Affiliation:
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Department of Orthopaedic Surgery, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA 19107, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Alginates / chemistry Animals Annexin A5 / pharmacology Apoptosis Biophysics / methods Blotting, Western Bone and Bones / cytology* Cell Size Cell Survival Flow Cytometry Glucuronic Acid / chemistry Gravity, Altered Hexuronic Acids / chemistry Humans Membrane Potentials Mice Mitochondria / pathology Musculoskeletal System Osteoblasts / metabolism, pathology* Phenotype Proto-Oncogene Proteins c-bcl-2 / metabolism RNA / chemistry Reverse Transcriptase Polymerase Chain Reaction Space Flight Staurosporine / pharmacology Stress, Mechanical Time Factors Weightlessness* Weightlessness Simulation |
| Chemical | |
Reg. No./Substance:
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0/Alginates; 0/Annexin A5; 0/Hexuronic Acids; 0/Proto-Oncogene Proteins c-bcl-2; 576-37-4/Glucuronic Acid; 62996-74-1/Staurosporine; 63231-63-0/RNA; 9005-32-7/alginic acid |
| Investigator | |
Investigator/Affiliation:
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I M Shapiro / Thomas Jefferson U, Philadelphia, PA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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