Interactive effects of PTH and mechanical stress on nitric oxide and PGE2 production by primary mouse osteoblastic cells.
Parathyroid hormone (PTH) and mechanical stress both stimulate bone formation but have opposite effects on bone resorption. PTH increased loading-induced bone formation in a rat model, suggesting that there is an interaction of these stimuli, possibly at the cellular level. To investigate whether PTH can modulate mechanotransduction by bone cells, we examined the effect of 10-9 M human PTH-(1-34) on fluid flow-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production by primary mouse osteoblastic cells in vitro. Mechanical stress applied by means of a pulsating fluid flow (PFF; 0.6 +/- 0.3 Pa at 5 Hz) stimulated both NO and PGE2 production twofold. In the absence of stress, PTH also caused a twofold increase in PGE2 production, but NO release was not affected and remained low. Simultaneous application of PFF and PTH nullified the stimulating effect of PFF on NO production, whereas PGE2 production was again stimulated only twofold. Treatment with PTH alone reduced NO synthase (NOS) enzyme activity to undetectable levels. We speculate that PTH prevents stress-induced NO production via the inhibition of NOS, which will also inhibit the NO-mediated upregulation of PGE2 by stress, leaving only the NO-independent PGE2 upregulation by PTH. These results suggest that mechanical loading and PTH interact at the level of mechanotransduction.
Bakker
Astrid D
AD
Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam, Vrije Universiteit, The Netherlands.
Joldersma
Manon
M
Klein-Nulend
Jenneke
J
Burger
Elisabeth H
EH
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011673:Pulsatile Flow / Q000502:physiology*; D013314:Stress, Mechanical; D019379:Teriparatide / Q000494:pharmacology*
D019379:Teriparatide; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D015232:Dinoprostone