PULSATING FLUID-FLOW STIMULATES PROSTAGLANDIN RELEASE AND INDUCIBLE PROSTAGLANDIN G H SYNTHASE MESSENGER-RNA EXPRESSION IN PRIMARY MOUSE BONE-CELLS/

Bone tissue responds to mechanical stress with adaptive changes in mas s and structure. Mechanical stress produces now of fluid in the osteoc yte lacunar-canalicular network, which is likely the physiological sig nal for bone ceh adaptive responses. We examined the effects of Ih pul sating fluid now (PFF; 0.7 +/- 0.02 Pa, 5 Hz) on prostaglandin (PG) E( 2), PGI(2), and PGF(2 alpha) production and on the expression of the c onstitutive and inducible prostaglandin G/H synthases, PGHS-1, and PGH S-2, the major enzymes in the conversion of arachidonic acid to prosta glandins, using mouse calvarial bone cell cultures. PFF treatment stim ulated the release of all three prostaglandins under 2% serum conditio ns, but with a different time course and to a different extent. PGF(2 alpha) was rapidly increased 5-10 minutes after the onset of PFF. PGE( 2) release increased somewhat more slowly (significant after 10 minute s), but continued throughout 60 minutes of treatment. The response of PGI(2) was the slowest, and only significant after 30 and 60 minutes o f treatment. In addition, PFF induced the expression of PGHS-2 but not PGHS-1. One hour of PFF treatment increased PGHS-2 mRNA expression ab out 2-fold relative to the induction by 2% fresh serum given at the st art of PFF. When the addition of fresh serum was reduced to 0.1%, the induction of PGHS-2 was 8- to 9-fold in PFF-treated cells relative to controls. This up-regulation continued for at least 1 h after PFF remo val. PFF also markedly increased PODS activity, measured as the conver sion of arachidonic acid into PGE(2). One hour after PFF removal, the production of all three prostaglandins was still enhanced. These resul ts suggest that prostaglandins are important early mediators of the re sponse of bone cells to mechanical stress. Prostaglandin up-regulation is associated with an induction of PGHS-2 enzyme mRNA, which may subs equently provide a means for amplifying the cellular response to mecha nical stress.