iNOS-Derived Nitric Oxide Stimulates Osteoclast Activity and Alveolar Bone Loss in Ligature-Induced Periodontitis in Rats

Autor(es)

Herrera, Bruno S. ^[1] ; Martins-Porto, Rodrigo ^[1] ; Maia-Dantas, Aline ^[1] ; Campi, Paula ^[1] ; Spolidorio, Luis C. ^[1] ; Costa, Soraia K. P. ^[1] ; Van Dyke, Thomas E. ^[2] ; Gyurko, Robert ^[2] ; Muscara, Marcelo N. ^[1]

Afiliação do(s) autor(es)

^[1] State Univ Sao Paulo, Dept Physiol & Pathol, Araraquara Dent Sch, BR-14801590 Araraquara, SP - Brazil

^[2] Boston Univ, Dept Periodontol & Oral Biol, Goldman Sch Dent Med, Boston, MA 02215 - USA

• Tipo de documento: Artigo Científico
• Fonte: Journal of Periodontology; v. 82, n. 11, p. 1608-1615, NOV 2011.
• Citações Web of Science: 33

Resumo

Background: Inflammatory stimuli activate inducible nitric oxide synthase (iNOS) in a variety of cell types, including osteoclasts (OC) and osteoblasts, resulting in sustained NO production. In this study, we evaluate the alveolar bone loss in rats with periodontitis under long-term iNOS inhibition, and the differentiation and activity of OC from iNOS-knockout (KO) mice in vitro. Methods: Oral aminoguanidine (an iNOS inhibitor) or water treatment was started 2 weeks before induction of periodontitis. Rats were sacrificed 3, 7, or 14 days after ligature placement, and alveolar bone loss was evaluated. In vitro OC culture experiments were also performed to study the differentiation of freshly isolated bone marrow cells from both iNOS KO and wild-type C57BL/6 mice. OC were counted 6 days later after tartrate-resistant acid phosphatase staining (a marker of osteoclast identity), and bone resorption activity was assessed by counting the number of resorption pits on dentin disks. Results: Rats with ligature showed progressive and significant alveolar bone loss compared to sham animals, and aminoguanidine treatment significantly inhibited ligature-induced bone loss at 7 and 14 days after the induction. In comparison to bone marrow cells from wild-type mice, cells from iNOS KO mice showed decreased OC growth and the resulting OC covered a smaller culture dish area and generated fewer resorption pit counts. Conclusion: Our results demonstrate that iNOS inhibition prevents alveolar bone loss in a rat model of ligature-induced periodontitis, thus confirming that iNOS-derived NO plays a crucial role in the pathogenesis of periodontitis, probably by stimulating OC differentiation and activity. J Periodontol 2011;82:1608-1615. (AU)

• Processo FAPESP: 02/10087-1 - Avaliacao do papel do oxido nitrico e especies relacionadas na doenca periodontal em ratos.
• Beneficiário: Bruno Schneider Herrera
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 08/02893-4 - Estabelecimento e padronização de culturas de osteoclastos e osteoblastos humanos como ferramenta para o estudo dos mecanismos envolvidos na perda óssea alveolar decorrente da periodontite
• Beneficiário: Bruno Schneider Herrera
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado