iNOS-derived nitric oxide modulates infection-stimulated bone loss.
Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) plays an important role in host defense, as well as in inflammation-induced tissue lesions. Here we evaluated the role of NO in bone loss in bacterial infection-induced apical periodontitis by using iNOS-deficient mice (iNOS(-/-)). The iNOS(-/-) mice developed greater inflammatory cell recruitment and osteolytic lesions than WT mice. Moreover, tartrate-resistant acid-phosphatase-positive (TRAP(+)) osteoclasts were significantly more numerous in iNOS(-/-) mice. Furthermore, the increased bone resorption in iNOS(-/-) mice also correlated with the increased expression of receptor activator NF-kappaB (RANK), stromal-cell-derived factor-1 alpha (SDF-1 alpha/CXCL12), and reduced expression of osteoprotegerin (OPG). These results show that NO deficiency was associated with an imbalance of bone-resorption-modulating factors, leading to severe infection-stimulated bone loss.
Fukada
S Y
SY
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, Monte Alegre, 14049-900, Ribeirão Preto SP, São Paulo, Brazil.
Silva
T A
TA
Saconato
I F
IF
Garlet
G P
GP
Avila-Campos
M J
MJ
Silva
J S
JS
Cunha
F Q
FQ
D000135:Acid Phosphatase / Q000032:analysis; D000196:Actinomycosis / Q000201:enzymology; D016301:Alveolar Bone Loss / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001424:Bacterial Infections / Q000201:enzymology*; D016866:Bacteroidaceae Infections / Q000201:enzymology; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000032:analysis; D003789:Dental Pulp Exposure / Q000382:microbiology; D007527:Isoenzymes / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010010:Osteoclasts / Q000473:pathology; D010014:Osteolysis / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin / Q000032:analysis; D010485:Periapical Periodontitis / Q000201:enzymology* / Q000473:pathology; D053245:RANK Ligand / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000032:analysis; D000071681:Tartrate-Resistant Acid Phosphatase
D015415:Biomarkers; D054377:Chemokine CXCL12; D007527:Isoenzymes; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase