Title: 0153 - Prevention of Periodontal Bone Loss by Homing and Inducing M2 Macrophages
Zhe Zhang, University of Pittsburgh
Sayuri Yoshizawa, University of Pittsburgh
Kostas Verdelis, University of Pittsburgh
Steve Little, University of Pittsburgh
Charles Sfeir (Presenter)
University of Pittsburgh
Objectives: Periodontitis is characterized by the progressive destruction of tooth-supporting alveolar bone and gingival soft tissues, which are mainly caused by chronic inflammation in response to persistent bacterial insult. Recently it has become clear that the pathogenesis of periodontitis is associated with the high ratio of pro-inflammatory M1 to anti-inflammatory M2 macrophages. The goal of this study was to promote chemotaxis of M0 (immature) or M2 (anti-inflammatory) macrophages to the inflamed site and induce M2 phenotype polarization locally. We used C-C motif chemokine ligand 2 (CCL2) known to recruit M0 macrophages, and induce differentiation of endogenous M2 macrophages.
Methods: We fabricated CCL2 controlled release microparticles (MPs) using poly (lactic-co-glycolic) acid. In vitro assessment for CCL2 release was performed and also the chemotaxis ability of CCL2. In addition, the effect of CCL2 delivery was assessed in vivo in both Porphyromonas gingivalis (Pg) induced and ligature induced murine periodontitis models.
Results: The expression of M2 macrophage marker CD206 was increased when mouse M0 macrophages were treated with CCL2. Also, the secretion level of TNF-alpha was decreased in LPS stimulated RAW 264.7 cells after CCL2 treatment. Moreover, enhanced chemotaxis of RAW264.7 cells towards CCL2 released from MPs was observed in Transwell plates. We administered CCL2 MPs into periodontal tissues of both Pg induced and ligature induced murine periodontitis models, and analyzed alveolar bone loss by microCT. The alveolar bone loss was significantly reduced in the CCL2 MPs treatment group, compared to blank MPs group and no treatment periodontitis group. Moreover, qPCR results showed a significant increase in IL1ra mRNA expression and decrease in RANKL mRNA expression in CCL2 MPSs group in ligature model.
Conclusions: Manipulation of endogenous M2 macrophages in vivo using CCL2 MPs in vivo, and prevented alveolar bone loss in mouse periodontitis models, is a novel immunological treatment approach for periodontitis.
This abstract is based on research that was funded entirely or partially by an outside source:
NIH R21 DE025735
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