Conclusions
Our study confirmed the central role of HGF in the pathogenesis of severe periodontitis in relevant in vitro and in vivo models. The positive effect of anti-HGF treatment provides a strong rationale for the use of anti-HGF-neutralizing antibodies for the treatment of human periodontitis.
Methods
Gingival tissues from cynomolgus monkeys, which naturally develop severe periodontitis, were isolated to establish an in vitro periodontitis model. Periodontitis-affected monkeys were treated by gingival injection of anti-HGF neutralizing antibodies. The therapeutic effects were documented by clinical examination (probing depth and bleeding on probing), histological examination of tissue, and reevaluation of gingival fibroblasts in the in vitro model.
Results
Periodontitis-affected monkeys contain periodontitis-associated fibroblasts (PAFs) with a pro-inflammatory phenotype that induced pronounced collagen degradation in vitro. This degradation was effectively inhibited by anti-HGF-neutralizing antibodies. Locally administered anti-HGF antibody to monkey gingiva clinically improved the severity of periodontitis. This was also reflected in the tissue histology with lower inflammatory cell infiltrates in treated gingiva than in non-treated gingiva. Moreover, fibroblasts isolated from anti-HGF-treated gingiva demonstrated reduced collagen degradation capacity. Conclusions: Our study confirmed the central role of HGF in the pathogenesis of severe periodontitis in relevant in vitro and in vivo models. The positive effect of anti-HGF treatment provides a strong rationale for the use of anti-HGF-neutralizing antibodies for the treatment of human periodontitis.