Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts--correlation with prostaglandin upregulation

Abstract

Osteocytes are extremely sensitive to fluid shear stress, a phenomenon that may be related to mechanical adaptation of bone (FASEB J 9:441,1995). Here we examined the effect of pulsating fluid flow (PFF, 0.5 +/- 0.02 Pa, 5 Hz, 0.4 Pa/sec) on the release of NO, in relation with upregulation of prostaglandin E2 (PGE2). Chicken calvarial osteocytes, but not periosteal fibroblasts, as well as mouse calvarial cells responded to PFF with a rapid and transient 2 to 3-fold stimulation of NO release. The effect was maximal after 5 min and leveled off thereafter. PFF also stimulated PGE2 release. This effect was significant after 10 min and continued throughout 60 min PFF treatment. Inhibition of NO release by NG-monomethyl-L-arginine prevented the effect of PFF on NO as well as PGE2 release. These results suggest that NO is a mediator of mechanical effects in bone, leading to enhanced PGE2 release. They further strengthen the hypothesis that fluid flow through the osteocyte canalicular network provides the physical stimulus for mechanosensation in bone.