Mechanisms controlling nitric oxide synthesis in osteoblasts.
Nitric oxide (NO) modulates the activity of a number of cell types, but little is known about its possible role in bone metabolism. In the present study we demonstrate that freshly isolated murine osteoblasts and an osteoblastic cell line express NO-synthase mRNA and release NO when stimulated with IL-1 or LPS, thus confirming the results of some recent reports using human and rat osteoblast-like cells. Synergistic effects were found between IL-1 and LPS or TNF. Enzyme induction was blocked by dexamethasone and IL-4. 1,25-dihydroxyvitamin D3 did not modify basal NO synthesis, but it markedly increased the cytokine-induced NO release. M-CSF, GM-CSF, IL-3, LIF, PTH, estradiol and calcitonin did not show significant effects on NO synthesis. NOS induction was blocked by various tyrosine-kinase inhibitors, geldanamycin and herbimycin A being the most potent. These results suggest that endogenous NO might participate in the regulation of bone remodeling at the local level, and may mediate some effects of vitamin D on bone. NO has recently been reported to inhibit osteoclastic bone resorption. The release of NO induced by bone-stimulating factors such as IL-1 may represent a protective mechanism helping to avoid excess resorption and preserve bone integrity in inflammatory conditions.
Riancho
J A
JA
Department of Internal Medicine, Hospital M. Valdecilla, University of Cantabria, Santander, Spain.
Zarrabeitia
M T
MT
Fernandez-Luna
J L
JL
Gonzalez-Macias
J
J
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016227:Benzoquinones; D016723:Bone Remodeling / Q000502:physiology; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger; D017828:Rifabutin / Q000031:analogs & derivatives; D012977:Sodium Nitrite / Q000494:pharmacology; D019379:Teriparatide; D014807:Vitamin D / Q000378:metabolism; D019323:omega-N-Methylarginine
D016227:Benzoquinones; D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011809:Quinones; D012333:RNA, Messenger; D019379:Teriparatide; D014807:Vitamin D; D017828:Rifabutin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004958:Estradiol; C020754:herbimycin; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D011505:Protein-Tyrosine Kinases; D012977:Sodium Nitrite; C001277:geldanamycin