Fluid flow stimulates rapid and continuous release of nitric oxide
in osteoblasts.
Johnson, Dameron L., Todd N. McAllister, and John A. Frangos.
Department of Bioengineering, University of California, San Diego,
La Jolla, Ca. 92093
APStracts 3:0085E, 1996.
Interstitial fluid flow may mediate skeletal remodeling in response to
mechanical loading. Since nitric oxide (NO) has been shown to be an
osteoblast mitogen and inhibitor of osteoclastic resorption, we
investigated and characterized the role of fluid shear on the release
of NO in osteoblasts. Rat calvarial cells in a stationary culture
produced undetectable levels of NO. Fluid shear stress (6 dyne/cm2)
rapidly increased NO release rate to 9.8 nmoles/hour/mg protein and
sustained this production for 12 hours of exposure to flow. Cytokine
treatment also induced NO synthesis after a 12 hour lag phase of zero
production, followed by a production rate of 0.6 nmoles/hour/mg
protein. Flow-induced NO production was blocked by the NO synthase
(NOS) inhibitor NG-amino-argininebut not by dexamethasone, which
suggests that the flow stimulated a constitutive NOS isoform. This is
the first time that a functional constitutively present NOS isoform
has been identified in osteoblasts. Moreover, fluid flow represents
the most potent stimulus of NO release in osteoblasts reported to
date. Fluid flow-induced NO production may therefore play a primary
role in bone maintenance and remodeling.
Received 5 February 1996; accepted in final form 1 April 1996.
APS Manuscript Number E70-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96