Gli1+ Periodontium Stem Cells Are Regulated by Osteocytes and Occlusal Force

• Published in: Developmental cell Vol. 54; no. 5; pp. 639 - 654.e6
• Main Authors: Men, Yi, Wang, Yuhong, Yi, Yating, Jing, Dian, Luo, Wenjing, Shen, Bo, Stenberg, William, Chai, Yang, Ge, Woo-Ping, Feng, Jian Q., Zhao, Hu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.09.2020
• Subjects: alveolar bone; Animals; Cell Differentiation - genetics; Cells, Cultured; dental stem cells; Gli1; mechanical force; Mice, Transgenic; Multipotent Stem Cells - cytology; Osteocytes - metabolism; periodontal ligament; Periodontal Ligament - cytology; periodontium; Periodontium - metabolism; Regeneration - physiology; Sclerostin; stem cells; Stem Cells - cytology; tooth; Wnt; Wnt Signaling Pathway - genetics; Zinc Finger Protein GLI1 - genetics; alveolar bone; stem cells; periodontium; Sclerostin; periodontal ligament; Gli1; mechanical force; Wnt; tooth; dental stem cells
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2020.06.006

Teeth are attached to alveolar bone by the periodontal ligament (PDL), which contains stem cells supporting tissue turnover. Here, we identified Gli1+ cells in adult mouse molar PDL as multi-potential stem cells (PDLSCs) giving rise to PDL, alveolar bone, and cementum. They support periodontium tissue turnover and injury repair. Gli1+ PDLSCs are surrounding the neurovascular bundle and more enriched in the apical region. Canonical Wnt signaling is essential for their activation. Alveolar bone osteocytes negatively regulate Gli1+ PDLSCs activity through sclerostin, a Wnt inhibitor. Blockage of sclerostin accelerates the PDLSCs lineage contribution rate in vivo. Sclerostin expression is modulated by physiological occlusal force. Removal of occlusal force upregulates sclerostin and inhibits PDLSCs activation. In summary, Gli1+ cells are the multipotential PDLSCs in vivo. Osteocytes provide negative feedback to PDLSCs and inhibit their activities through sclerostin. Physiological occlusal force indirectly regulates PDLSCs activities by fine-tuning this feedback loop. •Perivascular Gli1+ cells are stem cells (PDLSCs) for the periodontal tissue•Wnt signal is essential for PDLSC activity•Sclerostin secreted from bones represses Wnt and PDLSC activities•Biting force regulates PDLSC activity by modulating sclerostin level Teeth are suspended within alveolar bone through a fibrous tissue called periodontal ligament and are subject to biting force during mastication. Men et al. identify Gli1+ cells as periodontal stem cells (PDLSCs). PDLSCs surround the neurovascular bundle and are regulated by osteocytes and biting force.