LepR-expressing cells are a critical population in periodontal healing post periodontitis

Identification of promising seed cells plays a pivotal role in achieving tissue regeneration. This study demonstrated that LepR-expressing cells (LepR(+) cells) are required for maintaining periodontal homeostasis at the adult stage. We further investigated how LepR(+) cells behave in periodontal healing using a ligature-induced periodontitis (PD) and a self-healing murine model with LepR(Cre/+); R26R(tdTomato/+) mice. Lineage tracing experiments revealed that the largely suppressed osteogenic ability of LepR(+) cells results from periodontal inflammation. Periodontal defects were partially recovered when the ligature was removed, in which the osteogenic differentiation of LepR(+) cell lineage was promoted and contributed to the newly formed alveolar bone. A cell ablation model established with LepR(Cre/+); R26R(tdTomato/+); R26R(DTA/+) mice further proved that LepR(+) cells are an important cell source of newly formed alveolar bone. Expressions of beta-catenin and LEF1 in LepR(+) cells were upregulated when the inflammatory stimuli were removed, which are consistent with the functional changes observed during periodontal healing. Furthermore, the conditional upregulation of WNT signaling or the application of sclerostin neutralized antibody promoted the osteogenic function of LepR(+) cells. In contrast, the specific knockdown of beta-catenin in LepR(+) human periodontal ligament cells with small interfering RNA caused arrested osteogenic function. Our findings identified the LepR(+) cell lineage as a critical cell population for endogenous periodontal healing post PD, which is regulated by the WNT signaling pathway, making it a promising seed cell population in periodontal tissue regeneration. This study reveals the necessary role of the LepR(+) cell lineage in maintaining periodontal homeostasis during adulthood and in periodontal healing post periodontitis. The osteogenic differentiation ability of LepR(+) lineage cells is improved and contribute to periodontal healing, especially alveolar bone healing. In contrast, specific deletion of LepR(+) lineage cells results in hampered periodontal healing. Moreover, the osteogenic capacity of LepR(+) lineage cells is regulated by WNT signaling pathway. [GRAPHICS] .