Td92, an outer membrane protein of Treponema denticola, induces osteoclastogenesis via PGE2 mediatede RANKL/OPG regulation

Abstract

[한글]

[영문]Periodontitis is a chronic inflammatory disease in periodontium which causes significant alveolar bone loss. Osteoclasts are bone-resorbing multinucleated cells. Osteoclasts regulate osteoclast differentiation by receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) expression. Treponema denticola is one of the oral bateria involved in periodontitis. Td92, Tp92 homolog of T. denticola, is a surface-exposed outer membrane protein that stimulateds production of various proinflammatory mediators. However, the role of Td92 on alveolar bone resorption still remains unclear. To elucidate the role of Td92 on bone resorption, the effect of Td92 on osteoclast differentiation was evaluated in co-cultures of mouse calvariae-derived osteoblasts and bone marrow cells. The expression of RANKL, OPG, and PGE2 in osteoblasts was estimated by ELISA. Td92 induced osteoclast formation in co-cultures. In osteoblasts, RANKL and PGE2 expression was up-regulated while OPG expression was down-regulated by Td92. OPG inhibited Td92-induced osteoclast formation. NS398 or indomethacin, prostaglandin synthesis inhibitors, also inhibited Td92-induced osteoclast formation. The effect of Td92 on expression of RANKL, OPG, and PGE2 in osteoblasts was blocked by NS398 or indomethacin. These results suggest that Td92 promotes osteoclast formation through the regulation of RANKL and OPG productions via PGE2 dependent mechanism.