LepR-Expressing Stem Cells Are Essential for Alveolar Bone Regeneration

Stem cells play a critical role in bone regeneration. Multiple populations of skeletal stem cells have been identified in long bone, while their identity and functions in alveolar bone remain unclear. Here, we identified a quiescent leptin receptor-expressing (LepR⁺) cell population that contributed to intramembranous bone formation. Interestingly, these LepR⁺ cells became activated in response to tooth extraction and generated the majority of the newly formed bone in extraction sockets. In addition, genetic ablation of LepR⁺ cells attenuated extraction socket healing. The parabiosis experiments revealed that the LepR⁺ cells in the healing sockets were derived from resident tissue rather than peripheral blood circulation. Further studies on the mechanism suggested that these LepR⁺ cells were responsive to parathyroid hormone/parathyroid hormone 1 receptor (PTH/PTH1R) signaling. Collectively, we demonstrate that LepR⁺ cells, a postnatal skeletal stem cell population, are essential for alveolar bone regeneration of extraction sockets.