Periodontal disease, the leading cause of tooth loss in the adult population, is an inflammatory disease which is triggered by bacteria, but it is thought that periodontal tissue damage is primarily inflicted by the host's own defense reaction. Nitric oxide (NO) is a multifunctional molecule present in periodontal tissues, which can be toxic to bacteria as well as to cells of the periodontal tissue. NO is released in response to Porphyromonas gingivalis (P. gingivalis) infection, a bacterium which is clinically and experimentally associated with periodontal disease. We propose experiments to elucidate the role of NO in the defense against P. gingivalis infection. In preliminary studies we have compared P. gingivalis-induced periodontal bone loss in normal mice and in mutant mice which do not produce NO in response to bacteria (iNOS KO mice). We found that iNOS KO mice are resistant to P. gingivalis induced bone loss. To investigate the mechanisms by which NO participates in antimicrobial defense, the role of NO in inflammatory reaction is evaluated in an implant chamber model of P. gingivalis infection. We study the interaction of NO with other antibacterial molecules, such as superoxide, by testing mutant mice deficient in NO, superoxide, or both NO and superoxide. To assess the importance of NO in regulating bone destruction, isolated bone tissue from normal and iNOS KO mice is tested for a series of signaling molecules which are known to cause bone loss. The role of NO in bone development at various ages of normal and iNOS KO mice is also tested. Robert Gyurko, DDS, PhD is currently conducting research on the role of NO in cardiovascular diseases at the Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA. He is applying for the NIDCR Scholar Development and Faculty Transition Award to pursue scientific career as an independent investigator at Boston University School of Dental Medicine. ? ?

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Career Transition Award (K22)
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NIDCR Special Grants Review Committee (DSR)
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Hardwick, Kevin S
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Boston University
Schools of Dentistry
United States
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Herrera, Bruno S; Martins-Porto, Rodrigo; Campi, Paula et al. (2011) Local and cardiorenal effects of periodontitis in nitric oxide-deficient hypertensive rats. Arch Oral Biol 56:41-7
Herrera, Bruno S; Martins-Porto, Rodrigo; Maia-Dantas, Aline et al. (2011) iNOS-derived nitric oxide stimulates osteoclast activity and alveolar bone loss in ligature-induced periodontitis in rats. J Periodontol 82:1608-15
Gyurko, Robert; Siqueira, Camille C; Caldon, Nathaniel et al. (2006) Chronic hyperglycemia predisposes to exaggerated inflammatory response and leukocyte dysfunction in Akita mice. J Immunol 177:7250-6
Gyurko, R; Shoji, H; Battaglino, R A et al. (2005) Inducible nitric oxide synthase mediates bone development and P. gingivalis-induced alveolar bone loss. Bone 36:472-9
Gyurko, Robert; Boustany, Gabriel; Huang, Paul L et al. (2003) Mice lacking inducible nitric oxide synthase demonstrate impaired killing of Porphyromonas gingivalis. Infect Immun 71:4917-24