Title: 0154 - The Immunomodulatory Role of Wnt/β-catenin in Periodontal Tissue Regeneration
Yinghong Zhou (Presenter)
the Institute of Health and Biomedical Innovation, Queensland University of Technology
Saso Ivanovski, School of Dentistry, The University of Queensland
Yin Xiao, the Institute of Health and Biomedical Innovation, Queensland University of Technology
Objectives: Cells of the innate immune system, such as macrophages, are crucial for an effective host defence against pathogenic microorganisms in periodontal tissues. Growing evidence suggests that inflammation hampers the regenerative ability of periodontal ligament cells (PDLCs). Recent studies have shown that the activation of Wnt/β-catenin plays a crucial role in suppression of immune pathologies. The aim of this study is to understand the role of Wnt/β-catenin in regulating the local immune environment and its subsequent effect on periodontal tissue regeneration.
Methods: Standard periodontal defects were created in Lewis rats according to previously published protocol. LiCl (Wnt activator) was administered locally into the periodontal defect sites 12 hours after the surgery. Local injection of phosphate-buffered saline served as the control. Samples were harvested at 1 week and 2 weeks post-surgery and subjected to histological and immunohistochemical evaluation of macrophage distribution and phenotype (M1, pro-inflammatory and M2, anti-inflammatory). The murine macrophage cell line, RAW 264.7, was stimulated with LiCl at various concentrations to activate Wnt/β-catenin signal pathway in vitro. The PDLCs were treated with the conditioned medium derived from the LiCl-activated macrophages, and the gene expression related to osteogenesis and cementogenesis was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
Results: Significantly more macrophages gathered around the periodontal defects during early healing upon receiving Wnt/β-catenin signal cue. Less M1 macrophages and more M2 macrophages were present around the defect sites in week 2, accompanied with remarkable regeneration of alveolar bone and cementum in Wnt/β-catenin activation group. RT-qPCR analysis further confirmed a significant elevated expression levels of bone- and cementum-related genes in PDLCs stimulated with conditioned medium derived from LiCl-activated macrophages.
Conclusions: Wnt/β-catenin plays a crucial role in recruiting macrophages and regulating their phenotypic switching in favour of periodontal tissue repair and regeneration. Wnt/β-catenin pathway may be targeted for successful therapeutic interventions in periodontal diseases.
This abstract is based on research that was funded entirely or partially by an outside source:
The National Health and Medical Research Council, Australia
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE