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Ca(2+) regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblastsOsteoblasts subjected to fluid shear increase the expression of the early response gene, c-fos, and the inducible isoform of cyclooxygenase, COX-2, two proteins linked to the anabolic response of bone to mechanical stimulation, in vivo. These increases in gene expression are dependent on shear-induced actin stress fiber formation. Here, we demonstrate that MC3T3-E1 osteoblast-like cells respond to shear with a rapid increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) that we postulate is important to subsequent cellular responses to shear. To test this hypothesis, MC3T3-E1 cells were grown on glass slides coated with fibronectin and subjected to laminar fluid flow (12 dyn/cm(2)). Before application of shear, cells were treated with two Ca(2+) channel inhibitors or various blockers of intracellular Ca(2+) release for 0. 5-1 h. Although gadolinium, a mechanosensitive channel blocker, significantly reduced the [Ca(2+)](i) response, neither gadolinium nor nifedipine, an L-type channel Ca(2+) channel blocker, were able to block shear-induced stress fiber formation and increase in c-fos and COX-2 in MC3T3-E1 cells. However, 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, an intracellular Ca(2+) chelator, or thapsigargin, which empties intracellular Ca(2+) stores, completely inhibited stress fiber formation and c-fos/COX-2 production in sheared osteoblasts. Neomycin or U-73122 inhibition of phospholipase C, which mediates D-myo-inositol 1,4,5-trisphosphate (IP(3))-induced intracellular Ca(2+) release, also completely suppressed actin reorganization and c-fos/COX-2 production. Pretreatment of MC3T3-E1 cells with U-73343, the inactive isoform of U-73122, did not inhibit these shear-induced responses. These results suggest that IP(3)-mediated intracellular Ca(2+) release is required for modulating flow-induced responses in MC3T3-E1 cells.
Document ID
20040141577
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Chen, N. X.
(Indiana University School of Medicine Indianapolis, Indiana 46202, United States)
Ryder, K. D.
Pavalko, F. M.
Turner, C. H.
Burr, D. B.
Qiu, J.
Duncan, R. L.
Date Acquired
August 22, 2013
Publication Date
May 1, 2000
Publication Information
Publication: American journal of physiology. Cell physiology
Volume: 278
Issue: 5
ISSN: 0363-6143
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: T32 AR-07581
CONTRACT_GRANT: AR-43222
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Program Biomedical Research and Countermeasures
NASA Discipline Musculoskeletal

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