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Mechanically induced c-fos expression is mediated by cAMP in MC3T3-E1 osteoblastsIn serum-deprived MC3T3-E1 osteoblasts, mechanical stimulation caused by mild (287 x g) centrifugation induced a 10-fold increase in mRNA levels of the proto-oncogene, c-fos. Induction of c-fos was abolished by the cAMP-dependent protein kinase inhibitor H-89, suggesting that the transient c-fos mRNA increase is mediated by cAMP. Down-regulation of protein kinase C (PKC) activity by chronic TPA treatment failed to significantly reduce c-fos induction, suggesting that TPA-sensitive isoforms of PKC are not responsible for c-fos up-regulation. In addition, 287 x g centrifugation increased intracellular prostaglandin E2 (PGE2) levels 2.8-fold (P<0. 005). Since we have previously shown that prostaglandin E2 (PGE2) can induce c-fos expression via a cAMP-mediated mechanism, we asked whether the increase in c-fos mRNA was due to centrifugation-induced PGE2 release. Pretreatment with the cyclooxygenase inhibitors indomethacin and flurbiprofen did not hinder the early induction of c-fos by mechanical stimulation. We conclude that c-fos expression induced by mild mechanical loading is dependent primarily on cAMP, not PKC, and initial induction of c-fos is not necessarily dependent on the action of newly synthesized PGE2.
Document ID
20040150955
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Fitzgerald, J.
(Veterans Affairs Medical Center San Francisco, California 94121, United States)
Hughes-Fulford, M.
Date Acquired
August 22, 2013
Publication Date
March 1, 1999
Publication Information
Publication: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume: 13
Issue: 3
ISSN: 0892-6638
Subject Category
Life Sciences (General)
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Cell Biology

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