Td92, an outer membrane protein of Treponema denticola, induces osteoclastogenesis via prostaglandin E(2)-mediated RANKL/osteoprotegerin regulation.
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.


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 E(2) (PGE(2) ) in osteoblasts were estimated by ELISA.


RESULTS
Td92 induced osteoclast formation in the co-cultures. In the osteoblasts, RANKL and PGE(2) 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(2) in osteoblasts were blocked by NS398 or indomethacin.


CONCLUSIONS
These results suggest that Td92 promotes osteoclast formation through the regulation of RANKL and OPG production via a PGE(2) -dependent mechanism.
Kim
M
M
Department of Oral Biology, BK21 Project, Oral Science Research Center, Research Center for Orofacial Hard Tissue Regeneration, Yonsei University College of Dentistry, Seoul, Korea.
Jun
H-K
HK
Choi
B-K
BK
Cha
J-H
JH
Yoo
Y-J
YJ
D018829:Adhesins, Bacterial / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016301:Alveolar Bone Loss / Q000378:metabolism* / Q000382:microbiology; D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D018920:Coculture Techniques; D015232:Dinoprostone / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D008815:Mice, Inbred Strains; D010006:Osteoblasts; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D053244:Osteoprotegerin / Q000096:biosynthesis* / Q000235:genetics; D053245:RANK Ligand / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D048373:Treponema denticola / Q000737:chemistry* / Q000502:physiology
D018829:Adhesins, Bacterial; D053244:Osteoprotegerin; D053245:RANK Ligand; D011994:Recombinant Proteins; D015232:Dinoprostone