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Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactionsMechanical stimulation of bone induces new bone formation in vivo and increases the metabolic activity and gene expression of osteoblasts in culture. We investigated the role of the actin cytoskeleton and actin-membrane interactions in the transmission of mechanical signals leading to altered gene expression in cultured MC3T3-E1 osteoblasts. Application of fluid shear to osteoblasts caused reorganization of actin filaments into contractile stress fibers and involved recruitment of beta1-integrins and alpha-actinin to focal adhesions. Fluid shear also increased expression of two proteins linked to mechanotransduction in vivo, cyclooxygenase-2 (COX-2) and the early response gene product c-fos. Inhibition of actin stress fiber development by treatment of cells with cytochalasin D, by expression of a dominant negative form of the small GTPase Rho, or by microinjection into cells of a proteolytic fragment of alpha-actinin that inhibits alpha-actinin-mediated anchoring of actin filaments to integrins at the plasma membrane each blocked fluid-shear-induced gene expression in osteoblasts. We conclude that fluid shear-induced mechanical signaling in osteoblasts leads to increased expression of COX-2 and c-Fos through a mechanism that involves reorganization of the actin cytoskeleton. Thus Rho-mediated stress fiber formation and the alpha-actinin-dependent anchorage of stress fibers to integrins in focal adhesions may promote fluid shear-induced metabolic changes in bone cells.
Document ID
20040142149
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Pavalko, F. M.
(Indiana University School of Medicine Indianapolis, Indiana 46202, United States)
Chen, N. X.
Turner, C. H.
Burr, D. B.
Atkinson, S.
Hsieh, Y. F.
Qiu, J.
Duncan, R. L.
Date Acquired
August 22, 2013
Publication Date
December 1, 1998
Publication Information
Publication: The American journal of physiology
Volume: 275
Issue: 6 Pt 1
ISSN: 0002-9513
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: AR-43222
CONTRACT_GRANT: T32 AR-07581
CONTRACT_GRANT: GM-4733
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Musculoskeletal

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