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.

牙齿通过牙周韧带 (PDL) 附着在牙槽骨上，其中包含支持组织更新的干细胞。在这里，我们将成年小鼠磨牙 PDL 中的 Gli1+ 细胞鉴定为多潜能干细胞 (PDLSC)，从而产生 PDL、牙槽骨和牙骨质。它们支持牙周组织更新和损伤修复。Gli1+ PDLSCs 围绕在神经血管束周围，在顶端区域更丰富。规范 Wnt 信号传导对于它们的激活至关重要。牙槽骨骨细胞通过 Wnt 抑制剂 sclerostin 负向调节 Gli1+ PDLSCs 的活性。硬化蛋白的阻断加速了体内PDLSCs 谱系贡献率. 硬化蛋白的表达受生理咬合力的调节。去除咬合力上调硬化素并抑制 PDLSCs 活化。总之，Gli1+ 细胞是体内的多能 PDLSC 。骨细胞向 PDLSCs 提供负反馈并通过硬化素抑制它们的活动。生理咬合力通过微调这个反馈回路间接调节 PDLSCs 的活动。