Milk fat globule epidermal growth factor 8 inhibits periodontitis in non-human primates and its gingival crevicular fluid levels can differentiate periodontal health from disease in humans

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Tetsuhiro Kajikawa - , University of Pennsylvania (Author)
  • Fatimah Meshikhes - , University of Pennsylvania, King Fahad Specialist Hospital, Dammam (Author)
  • Tomoki Maekawa - , University of Pennsylvania, Niigata University (Author)
  • Evlambia Hajishengallis - , University of Pennsylvania (Author)
  • Kavita B. Hosur - , University of Pennsylvania (Author)
  • Toshiharu Abe - , University of Pennsylvania (Author)
  • Kevin Moss - , University of North Carolina at Chapel Hill (Author)
  • Triantafyllos Chavakis - , Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden (Author)
  • George Hajishengallis - , University of Pennsylvania (Author)

Abstract

Aim: We have previously shown that the secreted glycoprotein milk fat globule epidermal growth factor 8 (MFG-E8) has anti-inflammatory and anti-osteoclastogenic properties. Our objective was to investigate the potential of MFG-E8 as a diagnostic or therapeutic agent in periodontitis. Materials and Methods: Periodontitis was induced in non-human primates (NHPs) by placing ligatures around posterior teeth on both halves of the mandible for a split-mouth design: one side was treated with MFG-E8-Fc and the other with Fc control. Disease was assessed by clinical periodontal examinations, radiographic analysis of bone loss, and analysis of cytokine mRNA expression in gingival biopsy samples. Gingival crevicular fluid (GCF) was collected from human healthy volunteers or subjects with gingivitis, chronic moderate periodontitis, or chronic severe periodontitis. Additionally, GCF was collected from a subset of severe periodontitis patients following scaling and root planing (SRP) and after pocket reduction surgery. GCF was analysed to quantify MFG-E8 and periodontitis-relevant cytokines using multiplex assays. Results: In NHPs, sites treated with MFG-E8-Fc exhibited significantly less ligature-induced periodontal inflammation and bone loss than Fc control-treated sites. In humans, the GCF levels of MFG-E8 were significantly higher in health than in periodontitis, whereas the reverse was true for the proinflammatory cytokines tested. Consistently, MFG-E8 was elevated in GCF after both non-surgical (SRP) and surgical periodontal treatment of periodontitis patients. Conclusion: MFG-E8 is, in principle, a novel therapeutic agent and biomarker of periodontitis.

Details

Original languageEnglish
Pages (from-to)472-483
Number of pages12
JournalJournal of Clinical Periodontology
Volume44
Issue number5
Publication statusPublished - May 2017
Peer-reviewedYes

External IDs

Scopus 85017434244
PubMed 28207941

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • cytokines, inflammation, milk fat globule epidermal growth factor 8, non-human primates, periodontitis