Mechanical Force Regulates the PDL Stem Cells Activation

Objectives: Periodontal diseases are the most common reasons of tooth loss. Conventional treatments yield poor outcome on regenerating pathological periodontal tissue. Recent progress in stem cell biology have led to a promising novel therapy based on the ability PDL-derived stem cells to regenerate functioning periodontium. However, the further improvement of the stem cells based therapies are greatly impeded by the poor understanding of the PDL stem cells in vivo. There was little information about the in vivo localization, identity or regulating niche of the PDL stem cells. In this study, we are aiming to reveal the in vivo identity and regulating niche of periodontal mesenchymal stem cells.
Methods: Gli1-LacZ mouse model was used for analyzing the distribution pattern of Gli1+ cells. Gli1-CreERT2;Tdtomato mouse models were used for study the contribution of Gli1+ cells towards homoeostasis and injury repair. Axin2-LacZ model was used to analyze the Wnt activity within the PDL. Gli1-CreERT2;beta-catenin flox/flox model was used to study effects of loss of Wnt activity on the PDL tissue.
Results: We found out that PDL stem cells in the adult are mainly localized near the apical region of the teeth and can be labeled with Gli1. These Gli1+ stem cells are multipotential and give rise to the PDL, cementum and alveolar bone. They support both natural turnover and injury repair of the PDL tissue. Wnt signaling is critical for activation of PDL stem cells and blockage of Wnt signaling leads to severe periodontal tissue loss. Occlusal force regulates the activation of PDL MSCs. Removal of occlusal force leads to compromised activation of Gli1+ cells and other phenotypes.
Conclusions: Gli1+ cells are MSCs for the PDL tissue. Wnt signaling is critical for their activation and differentiation. Mechanical force also regulates the activation of Gli1+ cells, possibly by modulating the Wnt activity.