Subset of the periodontal ligament expressed leptin receptor contributes to part of hard tissue-forming cells.

The lineage of periodontal ligament (PDL) stem cells contributes to alveolar bone (AB) and cementum formation, which are essential for tooth-jawbone attachment. Leptin receptor (LepR), a skeletal stem cell marker, is expressed in PDL; however, the stem cell capacity of LepR PDL cells remains unclear. We used a Cre/LoxP-based approach and detected LepR-cre-labeled cells in the perivascular around the root apex; their number increased with age. In the juvenile stage, LepR PDL cells differentiated into AB-embedded osteocytes rather than cementocytes, but their contribution to both increased with age. The frequency of LepR PDL cell-derived lineages in hard tissue was < 20% per total cells at 1-year-old. Similarly, LepR PDL cells differentiated into osteocytes following tooth extraction, but their frequency was < 9%. Additionally, both LepR and LepR PDL cells demonstrated spheroid-forming capacity, which is an indicator of self-renewal. These results indicate that both LepR and LepR PDL populations contributed to hard tissue formation. LepR PDL cells increased the expression of LepR during spheroid formation, suggesting that the LepR PDL cells may hierarchically sit upstream of LepR PDL cells. Collectively, the origin of hard tissue-forming cells in the PDL is heterogeneous, some of which express LepR.