[P3-2-01] Blocking of osteocyte Toll-like receptor2-MyD88 signaling uncouples bone resorption from inflammation in periodontitis
Keywords:骨細胞、歯周病、TLRs-MyD88シグナル
Oral bacteria are potent inducers of bone resorption in periodontitis. As osteocytes express RANKL to activate osteoclasts, we proposed that osteocytes are the cellular mediators between bacterial infection and osteoclastogenesis. As we found that, like immune cells, osteocytes express Toll-like receptor 2 (TLR2) and its signal transducer MYD88, Dmp1-Cre;Myd88fl/fl mice were generated with targeted deletion of Myd88 in osteocytes. Inducing periodontitis by oral infection with Porphyromonas gingivalis (Pg, ATCC33277, 2x109 CFU) resulted in significantly less alveolar bone loss in Dmp1-Cre;Myd88fl/fl mice along with a decrease in Rankl expression in the jawbones, but no decrease in inflammation in the gingiva compared to Pg-infected Myd88fl/fl mice. Dmp1-Cre;Ranklfl/fl mice infected with Pg showed significant decrease in the alveolar bone loss compared to Ranklfl/fl mice infected with Pg, suggesting that RANKL in osteocytes is critical for the alveolar bone loss. Intraperitoneal administration of T6167923, an MYD88 inhibitor, protected against alveolar bone loss in the wild-type mice with Pg periodontitis. However, it did not affect the level of inflammation. In summary, our data show that blocking of osteocytic TLR2-MYD88 pathway uncouples bone resorption from inflammation in periodontitis. Bone destruction in periodontitis has been thought to be closely related to inflammation, but this study provides new insight into its pathogenesis.