Gli1+ Stem Cells Contribute to the Regeneration of Periodontal Tissues

Abstract

Periodontal diseases are mainly the result of infection and inflammation of the gingiva (gums), periodontal ligament (PDL), and alveolar bone that surround and support the teeth. 20-50% of the global population suffer from periodontal diseases, which lead to gum recession, alveolar bone loss and eventually tooth loss. Timely regeneration of injured periodontal tissues is an important prevention and treatment for periodontal tissue damage and disease. The periodontal crestal region (POCR) is the tip of gingival tissue near the tooth cervical region, which can be easily damaged as it is exposed to exogenous bacterial stimuli and serves as the first line protection for deeper periodontal tissues. Recently, we established a POCR-injury model and found that injured POCR can be regenerated. The POCR contains stem cells that can regenerate the PDL, gingiva and alveolar bone. In this study, we used a genetic lineage tracing approach to identify potential stem cells that participate in POCR regeneration in response to periodontal injury. We found that Gli1+ lineage cells contain POCR stem cells, which can contribute to gingival tissue, PDL and alveolar bone during normal homeostasis and expand after injury. Further study using the diphtheria toxin subunit A (DTA)-mediated cell ablation model to deplete the Gli1+ cells indicates that the Gli1 lineage cells are required for periodontal tissue turnover during homeostasis and periodontal tissue regeneration after injury.