Nitric oxide is an early mediator of the increase in bone formation by mechanical stimulation.
We tested the ability of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase (NOS), to suppress the osteogenic response in a recently developed model of mechanically induced osteogenesis. L-NMMA was given either as a single intraperitoneal dose, 15 min before the episode of mechanical stimulation, or as four doses every 6 h, commencing 2 h after loading. Administration of L-NMMA before loading completely prevented the increase in cancellous bone formation by mechanical stimulation. This suppression was largely lost when L-NMMA was administered after loading. Thus the response is likely to be due to activation of a preexistent constitutive NOS in bone cells during or very soon after mechanical stimulation. Suppression of the osteogenic response by L-NMMA was prevented by coadministration of L-arginine but not by the inactive isomer, D-arginine. These changes in cancellous bone were mirrored by similar changes on the corticoendosteal and periosteal bone surfaces. These data suggest that early release of NO is a key signal in the transduction of mechanical stimuli into subsequent bone formation.
Fox
S W
SW
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.
Chambers
T J
TJ
Chow
J W
JW
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007274:Injections, Intraperitoneal; D007536:Isomerism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase