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Publication : Antibody to receptor activator of NF-κB ligand ameliorates T cell-mediated periodontal bone resorption.

First Author  Lin X Year  2011
Journal  Infect Immun Volume  79
Issue  2 Pages  911-7
PubMed ID  21078845 Mgi Jnum  J:168604
Mgi Id  MGI:4889043 Doi  10.1128/IAI.00944-10
Citation  Lin X, et al. (2011) Antibody to receptor activator of NF-kappaB ligand ameliorates T cell-mediated periodontal bone resorption. Infect Immun 79(2):911-7
abstractText  Activated T and B lymphocytes in periodontal disease lesions express receptor activator of NF-kappaB ligand (RANKL), which induces osteoclastic bone resorption. The objective of this study was to evaluate the effects of anti-RANKL antibody on periodontal bone resorption in vitro and in vivo. Aggregatibacter actinomycetemcomitans outer membrane protein 29 (Omp29) and A. actinomycetemcomitans lipopolysaccharide (LPS) were injected into 3 palatal gingival sites, and Omp29-specific T clone cells were transferred into the tail veins of rats. Rabbit anti-RANKL IgG antibody or F(ab') antibody fragments thereof were injected into the palatal sites in each rat (days -1, 1, and 3). Anti-RANKL IgG antibody significantly inhibited soluble RANKL (sRANKL)-induced osteoclastogenesis in vitro, in a dose-dependent manner, but also gave rise to a rat antibody response to rabbit IgG in vivo, with no significant inhibition of periodontal bone resorption detected. Lower doses (1.5 and 0.15 mug/3 sites) of F(ab') antibody were not immunogenic in the context of the experimental model. Periodontal bone resorption was inhibited significantly by injection of the anti-RANKL F(ab') antibody into gingivae. The sRANKL concentrations for the antibody-treated groups were decreased significantly compared to those for the untreated group. Osteoclasts on the alveolar bone surface were also diminished significantly after antibody injection. Gingival sRANKL concentration and bone loss showed a significant correlation with one another in animals receiving anti-RANKL F(ab') antibody. These results suggest that antibody to RANKL can inhibit A. actinomycetemcomitans-specific T cell-induced periodontal bone resorption by blockade and reduction of tissue sRANKL, providing an immunological approach to ameliorate immune cell-mediated periodontal bone resorption.
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