1488 Anti-TACE antibody inhibits age-related and ligature-induced periodontal bone loss

Saturday, March 24, 2012: 9:45 a.m. - 11 a.m.
Presentation Type: Poster Session
M. SUZUKI, Immunology, Forsyth Institute, Cambridge, MA, H. KANZAKI, Div. of Orthodontics and Dentofacial Orthopedics, Tohoku University, Aoba-ku, Sendai, Miyagi, Japan, T. KAWAI, Forsyth Institute, Cambridge, MA, X. HAN, Department of Immunology, Forsyth Institute, Cambridge, MA, and M. TAUBMAN, The Forsyth Institute, Cambridge, MA
Objectives: TNF-alpha-Converting Enzyme (TACE), which cleaves membrane-bound RANKL to release soluble RANKL (sRANKL), can play a role in maintaining osteoclastogenesis. Previously, we demonstrated that administration of anti-TACE antibody (αTACE) to rats significantly inhibited T cell-mediated periodontal bone loss (PBL). We evaluated the effects of αTACE on age-related (Exp.1) and on ligature-induced (Exp.2) experimental PBL.

Methods: Exp.1: Rowett rats (6 months) divided into 4 groups. G1:(uninfected, no treatment), G2-4: infected with 108 P. gingivalis (Pg,W83) days 1-4. G2:(no treatment), G3:(Right side (R):αTACE injection 3 palatal sites, d9, 14, 21); Left side (L):PBS injection), G4 (R:αTACE passive application d9, 14, 21;L:PBS passive). After 4 weeks, all animals were euthanized. Exp.2: Rowett rats (3 months) divided into 4 groups. Animals treated with ligatures soaked with Pg (R:G1,G2,G3) or without Pg (L:G1,G4) in the maxillary 2nd molar. G1 (no treatment), G2 (R:αTACE injection; L:PBS injection d1,3), G3 (R:IgG injection, L:PBS injection), G4 (R:αTACE injection, L:PBS injection). Animals were euthanized after 15 days. PBL as CEJ to alveolar crest of R (treated side) was compared to L (control).

Results: There were no differences in bone loss between uninfected and Pg infected animals indicating this was not infection-induced PBL. Only group 3 demonstrated significant difference from the αTACE injected side (R) lower vs. PBS (L) (p=0.035). sRANKL concentration was significantly reduced in gingival tissue extracts from αTACE injected side(p=0.04) as TNF-α(p=0.004). In Exp.2, PBL was equal in ligatures with or without Pg. PBL was significantly reduced(p=0.016) in αTACE injection vs. PBS. sRANKL concentration in gingival extracts from αTACE injection were lower than all other treated controls.

Conclusions: αTACE injection reduced T-cell-mediated, age-related, and ligature-induced PBL. In αTACE injected cases gingival tissue extracts demonstrated less sRANKL than controls suggesting that RANKL was involved in each type of PBL which could be ameliorated by αTACE.

This abstract is based on research that was funded entirely or partially by an outside source: DE 03420

Keywords: Animal, Bone, Immunology, Periodontal disease and TACE
See more of: Immunology
See more of: Microbiology / Immunology