Gli1⁺ Periodontal Mesenchymal Stem Cells in Periodontitis

Periodontal mesenchymal stem cells (MSCs) play a crucial role in maintaining periodontium homeostasis and in tissue repair. However, little is known about how periodontal MSCs in vivo respond under periodontal disease conditions, posing a challenge for periodontium tissue regeneration. In this study, Gli1 was used as a periodontal MSC marker and combined with a Gli1-cre ERT2 mouse model for lineage tracing to investigate periodontal MSC fate in an induced periodontitis model. Our findings show significant changes in the number and contribution of Gli1⁺ MSCs within the inflamed periodontium. The number of Gli1⁺ MSCs that contributed to periodontal ligament homeostasis decreased in the periodontitis-induced teeth. While the proliferation of Gli1⁺ MSCs had no significant difference between the periodontitis and the control groups, more Gli1⁺ MSCs underwent apoptosis in diseased teeth. In addition, the number of Gli1⁺ MSCs for osteogenic differentiation decreased during the progression of periodontitis. Following tooth extraction, the contribution of Gli1⁺ MSCs to the tooth socket repair was significantly reduced in the periodontitis-induced teeth. Collectively, these findings indicate that the function of Gli1⁺ MSCs in periodontitis was compromised, including reduced contribution to periodontium homeostasis and impaired injury response.