title: Bone anabolic responses to mechanical load in vitro involve COX-2 and constitutive NOS.
abstract: Mechanical stimulation is essential for maintaining the homeostasis and architecture of connective tissues including bone. The purpose of our study was to test the importance of several potential signaling intermediates in the anabolic responses of bone to loads applied with a newly developed micromechanical loading device. Tibial bones excised from 7- to 8-day-old CD-1 mice were cyclically loaded at 1 Hz, 1000 muepsilon (microstrain) at a peak load of 100 mN. DNA and protein synthesis were evaluated by measuring the incorporation of 3H-thymidine and 14C-proline, respectively. The roles of cyclooxygenase (COX) isoforms, nitric oxide synthase (NOS) isoforms, and glutamate receptor-gated Ca2+ channeling were examined by incubating the bones in the presence of each of their specific inhibitors. The results indicate that COX-2 and constitutive NOS are important signaling molecules in the anabolic responses of neonatal tibial bone to the micromechanical load in vitro.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Kunnel
authors.forename: K
authors.initials: K
authors.lastname: Igarashi
authors.forename: J L
authors.initials: JL
authors.lastname: Gilbert
authors.forename: P H
authors.initials: PH
authors.lastname: Stern
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004867:Equipment Design; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013977:Tibia / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D016474:Weight-Bearing / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin