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

다국어 초록 (Multilingual Abstract)

<P><I>Kim M, Jun H-K, Choi B-K, Cha J-H, Yoo Y-J. Td92, an outer membrane protein of</I> Treponema denticola<I>, induces osteoclastogenesis via prostaglandin E</I><SUB><I>2</I></SUB><I>-mediated RANKL/osteoprotegerin regulation. J Periodont Res 2010; 45: 772–779. © 2010 John Wiley & Sons A/S</I></P><P>Background and Objective: </P><P>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 <I>Treponema denticola</I>, 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.</P><P>Material and Methods: </P><P>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 E<SUB>2</SUB> (PGE<SUB>2</SUB>) in osteoblasts were estimated by ELISA.</P><P>Results: </P><P>Td92 induced osteoclast formation in the co-cultures. In the osteoblasts, RANKL and PGE<SUB>2</SUB> 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 PGE<SUB>2</SUB> in osteoblasts were blocked by NS398 or indomethacin.</P><P>Conclusion: </P><P>These results suggest that Td92 promotes osteoclast formation through the regulation of RANKL and OPG production via a PGE<SUB>2</SUB>-dependent mechanism.</P>