Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways

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McAllister, T. N.¹; Frangos, J. A.¹

Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways

J Bone Miner Res. June 1999;14(6):930-936

©2021 American Society for Bone and Mineral Research

Affiliations

¹Department of Bioengineering, University of California–San Diego, La Jolla, California, U.S.A.
Abstract

Fluid flow has been shown to be a potent stimulus in osteoblasts and osteocytes and may therefore play an important role in load‐induced bone remodeling. The objective of this study was to investigate the characteristics of flow‐activated pathways. Previously we reported that fluid flow stimulates rapid and continuous release of nitric oxide (NO) in primary rat calvarial osteoblasts. Here we demonstrate that flow‐induced NO release is mediated by shear stress and that this response is distinctly biphasic. Transients in shear stress associated with the onset of flow stimulated a burst in NO production (8.2 nmol/mg of protein/h), while steady flow stimulated sustained NO production (2.2 nmol/mg of protein/h). Both G‐protein inhibition and calcium chelation abolished the burst phase but had no effect on sustained production. Activation of G‐proteins stimulated dose‐dependent NO release in static cultures of both calvarial osteoblasts and UMR‐106 osteoblast‐like cells. Pertussis toxin had no effect on NO release. Calcium ionophore stimulated low levels of NO production within 15 minutes but had no effect on sustained production. Taken together, these data suggest that fluid shear stress stimulates NO release by two distinct pathways: a G‐protein and calcium‐dependent phase sensitive to flow transients, and a G‐protein and calcium‐independent pathway stimulated by sustained flow.
Links

DOI: 10.1359/jbmr.1999.14.6.930

PubMed: 10352101

WoS: 000080615500011
History

Received: 1998-08-28

Revised: 1998-11-20

Accepted: 1998-12-30

Online: 1999-06-1

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