Macrophages contribute to periodontal wound healing mainly in the tissue proliferation stage
Bin Chen, Songying Li, Ya-Qin Chang, Jiading Zhang, Jiaying Liu, Yingchun Dong, Fuhua Yan
Abstract
OBJECTIVE: The aim of this study was to determine the preliminary role of macrophages in different stages of periodontal healing. BACKGROUND: Macrophages are promising target cells for periodontal regeneration. However, the stage at which they play a more important role during periodontal repair has not been elucidated till date. METHODS: First, the dynamic changes in M1 and M2 macrophages were analyzed in a rat periodontal-defect model at Days 1, 3, 5, 7, 14, 21, and 28 post-surgery. Macrophages were then depleted after 1, 6, and 14 days of surgery, and the healing results were evaluated via micro-computed tomography and histopathological detection. Finally, the effects of M1 and M2 macrophages on the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) were verified in vitro. RESULTS: During natural periodontal healing, the number of M1 macrophages increased the most during the early stage of healing (3 days post-operation), and subsequently, it decreased rapidly. The number of M2 macrophages was at its peak during the middle and late stages of tissue healing (5-21 days post-surgery). Interestingly, the highest number of M2 macrophages was observed at 5-14 days post-operation in the alveolar bone, while it was observed at 21 days post-operation in the cementum area. On the first and 14th day post-operation, the clearance of macrophages had no significant effect on tissue healing; however, on the sixth day post-operation, macrophage depletion significantly inhibited tissue regeneration (p < .05). In vitro studies showed that M2 macrophages, rather than M1 macrophages, could significantly promote the proliferation of MSCs (p < .01). CONCLUSION: It is better to intervene in tissue proliferation phase when a M2 macrophage regulation-based periodontal regenerative therapy is planned in the future.