Journal
JOURNAL OF APPLIED PHYSIOLOGY
Volume 96, Issue 3, Pages 957-966Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00869.2003
Keywords
osteoblasts; bone; stress-strain; mechanical loading
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Funding
- NIAMS NIH HHS [R01 AR049728-03, R01 AR-49728, R01 AR049728, P01 AR-45218] Funding Source: Medline
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Cultured osteoblasts express three major types of cytoskeleton: actin microfilaments, microtubules, and intermediate filaments. The cytoskeletal network is thought to play an important role in the transmission and conversion of a mechanical stimulus into a biochemical response. To examine a role for the three different cytoskeletal networks in fluid shear stress-induced signaling in osteoblasts, we individually disrupted actin microfilaments, microtubules, and intermediate filaments in MC3T3-E1 osteoblasts with multiple pharmacological agents. We subjected these cells to 90 min of laminar fluid shear stress (10 dyn/cm(2)) and compared the PGE(2) and PGI(2) release and induction of cyclooxygenase-2 protein to control cells with intact cytoskeletons. Disruption of actin microfilaments, microtubules, or intermediate filaments in MC3T3-E1 cells did not prevent a significant fluid shear stress- induced release of PGE(2) or PGI(2). Furthermore, disruption of actin microfilaments or microtubules did not prevent a significant fluid shear stress- induced increase in cyclooxygenase-2 protein levels. Disruption of intermediate filaments with acrylamide did prevent the fluid shear stress- induced increase in cyclooxygenase-2 but also prevented a PGE(2)-induced increase in cyclooxygenase-2. Thus none of the three major cytoskeletal networks are required for fluid shear stress- induced prostaglandin release. Furthermore, although neither actin microfilaments nor microtubules are required for fluid shear stress- induced increase in cyclooxygenase-2 levels, the role of intermediate filaments in regulation of cyclooxygenase-2 expression is less clear.
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