|Bone cell survival in microgravity: evidence that modeled microgravity increases osteoblast sensitivity to apoptogens.|
|PMID: 15644346 Owner: NLM Status: MEDLINE|
|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.|
|M A Bucaro; J Fertala; C S Adams; M Steinbeck; P Ayyaswamy; K Mukundakrishnan; I M Shapiro; M V Risbud|
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|Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.|
|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|
|Created Date: 2005-01-12 Completed Date: 2005-02-18 Revised Date: 2006-11-15|
Medline Journal Info:
|Nlm Unique ID: 7506858 Medline TA: Ann N Y Acad Sci Country: United States|
|Languages: eng Pagination: 64-73 Citation Subset: IM; S|
|Department of Orthopaedic Surgery, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA 19107, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Alginates / chemistry
Annexin A5 / pharmacology
Biophysics / methods
Bone and Bones / cytology*
Glucuronic Acid / chemistry
Hexuronic Acids / chemistry
Mitochondria / pathology
Osteoblasts / metabolism, pathology*
Proto-Oncogene Proteins c-bcl-2 / metabolism
RNA / chemistry
Reverse Transcriptase Polymerase Chain Reaction
Staurosporine / pharmacology
|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|
|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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