Abstract
The interaction between immune cells and stem cells is important during tissue repair. Macrophages have been described as being crucial for limb regeneration and in certain circumstances have been shown to affect stem cell differentiation in vivo. Dentine is susceptible to damage as a result of caries, pulp infection and inflammation all of which are major problems in tooth restoration. Characterising the interplay between immune cells and stem cells is crucial to understand how to improve natural repair mechanisms. In this study, we used an in vivo damage model, associated with a macrophage and neutrophil depletion model to investigate the role of immune cells in reparative dentine formation. In addition, we investigated the effect of elevating the Wnt/β-catenin pathway to understand how this might regulate macrophages and impact upon Wnt receiving pulp stem cells during repair. Our results show that macrophages are required for dental pulp stem cell activation and appropriate reparative dentine formation. In addition, pharmacological stimulation of the Wnt/β-catenin pathway via GSK-3β inhibitor small molecules polarises macrophages to an anti-inflammatory state faster than inert calcium silicate-based materials thereby accelerating stem cell activation and repair. Wnt/β-catenin signalling thus has a dual role in promoting reparative dentine formation by activating pulp stem cells and promoting an anti-inflammatory macrophage response.
Highlights
The interaction between immune cells and stem cells is important during tissue repair
Damaged teeth were analysed to verify the effect of modification of the macrophage population on reparative dentine formation (Fig. 1)
Having shown that macrophage reduction affects reparative dentine formation, we investigated whether neutrophil reduction affects dentine repair formation
Summary
The interaction between immune cells and stem cells is important during tissue repair. We used an in vivo damage model, associated with a macrophage and neutrophil depletion model to investigate the role of immune cells in reparative dentine formation. Our results show that macrophages are required for dental pulp stem cell activation and appropriate reparative dentine formation. Wnt/β-catenin signalling has a dual role in promoting reparative dentine formation by activating pulp stem cells and promoting an anti-inflammatory macrophage response. We used a small molecule GSK-3β antagonist (BIO, Merck), proven to enhance reparative dentine secretion via Wnt/β-catenin pathway activation, and compared it with a commonly used direct capping material (MTA, ProRoot Dentsply), to evaluate the biological differences between biological and inert direct capping in dental pulp immune reactions
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