IADR Abstract Archives

Topical OPG-Fc ameliorates RANKL-dependent rat periodontal bone-loss possibly involving FcRn

OBJECTIVES: Neonatal Fc receptor (FcRn) is known to play a pivotal role in maternal IgG transportation across the placenta during pregnancy. We discovered that FcRn is also expressed in both human and rat gingival epithelial cells. Our research further points to OPG-Fc as a potent inhibitor of RANKL. Therefore, this study examines whether 1) IgG-Fc-conjugated fusion protein, OPG-Fc, can be transported across gingival epithelium via FcRn and, if so, whether 2) its topical application to gingiva can inhibit RANKL-mediated bone loss.

METHODS: Immunohistochemical staining was employed to determine the expression of FcRn-protein in rat and mouse gingival epithelium. FcRn-KO mice were compared to their wild-type mice to examine the transport of topically applied OPG-Fc in vivo from oral cavity to gingival lamina propria. OPG-Fc contained in gingival tissue homogenates was quantitated by an ELISA system. Effects of topical gingival application of OPG-Fc on RANKL-mediated periodontal bone loss were examined using a rat periodontitis model.

RESULTS: In wild type (intact FcRn) mice, FcRn-protein was specifically found in gingival epithelium and OPG-Fc transport to gingival lamina propria was significantly greater than in FcRn-KO mice, implying that FcRn might be involved in transport of OPG-Fc to gingival lamina propria. Topical gingival application of OPG-Fc in a rat periodontitis model inhibited RANKL-mediated bone resorption (53%). Most importantly, co-localization of OPG-Fc and FcRn in the gingival epithelium was detected by fluorescent confocal microscopy. These results suggested that FcRn expressed in gingival epithelium may partake in transport of OPG-Fc to gingival lamina propria resulting in amelioration of bone resorption.

CONCLUSION: These results implied that FcRn expressed in gingival epithelial cells may facilitate non-invasive-delivery of Fc-conjugated fusion compounds (OPG-Fc in this study) to ameliorate the pathogenic complications of periodontal disease. Supported by IADR-GSK.


IADR/CADR General Session
2008 IADR/CADR General Session (Toronto, Ontario, Canada)
Toronto, Ontario, Canada
2008
59
Microbiology / Immunology and Infection Control
  • Kawai, Toshihisa  ( Forsyth Institute, Boston, MA, USA )
  • Ouhara, Kazuhisa  ( Forsyth Institute, Boston, MA, USA )
  • Stashenko, Philip  ( Forsyth Institute, Boston, MA, USA )
  • Taubman, Martin  ( Forsyth Institute, Boston, MA, USA )
    • Oral Session
    Immune Mechanisms
    07/02/2008