Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions

Fredrick Pavalko, Xuening (Neal) Chen, Charles H. Turner, David Burr, Simon Atkinson, Yeou Fang Hsieh, Jinya Qiu, Randall L. Duncan

Research output: Contribution to journalArticle

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Abstract

Mechanical 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 β1-integrins and α- 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 α-actinin that inhibits α-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 α-actinin-dependent anchorage of stress fibers to integrins in focal adhesions may promote fluid shear-induced metabolic changes in bone cells.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume275
Issue number6 44-6
StatePublished - 1998

Fingerprint

Osteoblasts
Actinin
Cytoskeleton
Stress Fibers
Integrins
Actins
Actin Cytoskeleton
Fluids
Gene expression
Focal Adhesions
Cyclooxygenase 2
Bone
Gene Expression
Fibers
fos Genes
Adhesion
Bone and Bones
Cytochalasin D
Monomeric GTP-Binding Proteins
Microinjections

Keywords

  • α-actinin
  • Gene expression
  • Mechanotransduction

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions. / Pavalko, Fredrick; Chen, Xuening (Neal); Turner, Charles H.; Burr, David; Atkinson, Simon; Hsieh, Yeou Fang; Qiu, Jinya; Duncan, Randall L.

In: American Journal of Physiology - Cell Physiology, Vol. 275, No. 6 44-6, 1998.

Research output: Contribution to journalArticle

Pavalko, Fredrick ; Chen, Xuening (Neal) ; Turner, Charles H. ; Burr, David ; Atkinson, Simon ; Hsieh, Yeou Fang ; Qiu, Jinya ; Duncan, Randall L. / Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions. In: American Journal of Physiology - Cell Physiology. 1998 ; Vol. 275, No. 6 44-6.
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AU - Pavalko, Fredrick

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AU - Atkinson, Simon

AU - Hsieh, Yeou Fang

AU - Qiu, Jinya

AU - Duncan, Randall L.

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