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

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 2^nd 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.