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, stem cell capacity of LepR + PDL is unclear. We used a Cre/LoxP-based approach and showed that LepR-cre-labeled cells were specifically detected in the perivascular area around the root apex, and 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-derived lineages in hard tissue was less than 20% per total cells at 1-year-old. Similarly, LepR + PDL differentiated into osteocytes after tooth extraction, but their frequency was less than 9%. Additionally, both LepR + and LepR − PDL demonstrated spheroid-forming capacity, which is an indicator of stem cell self-renewal potential in vitro . These results indicate that both lineages from LepR + and LepR − PDL populations contributed to AB and cementum formation. LepR − PDL increased the expression of LepR during spheroid formation, suggesting that the LepR − PDL sits hierarchically upstream of LepR + PDL. Collectively, the origin of hard tissue-forming cells in the PDL is heterogeneous, some of which express LepR.