Td92, an outer membrane protein of Treponema denticola, induces osteoclastogenesis via prostaglandin-E₂-mediated RANKL/osteoprotegerin regulation

Background and Objective: Periodontitis is a chronic inflammatory disease of the periodontium that causes significant alveolar bone loss. Osteoclasts are bone-resorbing multinucleated cells. Osteoblasts regulate osteoclast differentiation by expression of RANKL and osteoprotegerin (OPG). Td92 is a surface-exposed outer membrane protein of Treponema denticola, a periodontopathogen. Although it has been demonstrated that Td92 acts as a stimulator of various proinflammatory mediators, the role of Td92 in alveolar bone resorption remains unclear. Therefore, in this study, we investigated the role of Td92 in bone resorption.Material and Methods: Mouse bone marrow cells were co-cultured with calvariae-derived osteoblasts in the presence or absence of Td92. Osteoclast formation was assessed by TRAP staining. Expressions of RANKL, osteoprotegerin (OPG) and prostaglandin-E₂ (PGE₂) in osteoblasts were estimated by ELISA.Results: Td92 induced osteoclast formation in the co-cultures. In the osteoblasts, RANKL and PGE₂ expressions were up-regulated, whereas OPG expression was down-regulated by Td92. The addition of OPG inhibited Td92-induced osteoclast formation. The prostaglandin synthesis inhibitors NS398 and indomethacin were also shown to inhibit Td92-induced osteoclast formation. The effects of Td92 on the expressions of RANKL, OPG and PGE₂ in osteoblasts were blocked by NS398 or indomethacin. Conclusion: These results suggest that Td92 promotes osteoclast formation through the regulation of RANKL and OPG production via a PGE₂-dependent mechanism.