Oral Presentation 6th Australian Health and Medical Research Congress 2012

Epigenetic Control of Inflammation and Bone Loss using Histone Deacetylase Inhibitors. (#205)

Melissa D Cantley 1 , David P Fairlie 2 , Victor Marino 3 , Mark Bartold 3 , David R Haynes 1
  1. Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, SA, Australia
  2. Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia
  3. Colgate Australian Clinical Dental Research Centre, University of Adelaide, Adelaide, SA, Australia

Introduction: Histone deacetylase inhibitors (HDACi) are used to treat a wide variety of diseases. We have shown a novel broad acting HDACi, 1179.4b suppresses bone loss in a mouse model of periodontitis despite no effect on inflammation  (1). This suggests mechanisms controlling inflammation and bone loss may be different. The aim of this study was to assess the effects of 1179.4b on inflammation and bone loss in a mouse model of inflammatory arthritis. It is recognized that periodontitis and rheumatoid arthritis (RA) are related diseases (2) so it was hypothesized that 1179.4b would also suppress of bone loss in arthritis. This study also compared 1179.4b to a novel HDACi targeting HDAC 1 (NW-21). In addition, HDAC expression (HDACs 1-10) in human periodontitis tissues was investigated and compared to that reported in human RA tissues (3). Methods: Inflammatory arthritis was induced using the collagen antibody induced arthritis (CAIA) model (2). Live animal micro CT scans were conducted through out the experiment and histological assessments of and histology conducted on the front paws. HDAC expression in normal (n=8) and periodontitis (n=9) human gingival tissues were assessed using RT-PCR and immunohistochemistry. Results: Unexpectedly, HDACi 1179.4b did not suppress inflammation or bone loss in the arthritis model. However, HDACi NW-21 did reduce inflammation but only weakly suppressed bone loss. HDACs 1,5,8 and 9 were significantly up regulated in human periodontitis tissues. This was markedly different from RA where only HDAC1 was reported to be elevated. Conclusion: The results of this study suggest that despite similarities in periodontitis and RA there are differences in the HDAC control of bone loss and inflammation. This contention was supported by our finding that HDAC expression in human periodontitis was different to previously reported RA expression.

  1. Cantley et al. 2011 J. Periodontal Res; 46(6):697-703
  2. Cantley et al 2011. J Clin Periodontol; 38(6):532-41.
  3. Horiuchi et al 2009. J Rheumatol. 36:1580-9.