AbstractObjectiveto investigate whether harmine has a promotive effect on human periodontal ligament cells (hPDLCs)‐induced tissue regeneration.Materials and MethodsVarious concentrations of harmine on hPDLCs proliferation were tested. Osteogenic and cementogenic characteristics were examined in hPDLC/rhBMP‐2 and hPDLC/harmine by alizarin red S staining, real‐time PCR, and Western blotting assay. The activity of harmine was investigated in an ectopic transplantation nude mouse model.ResultsWe determined that 10 μM of harmine was the threshold concentration. hPDLC/harmine showed similar mineralized nodule formation in alizarin S staining compared to hPDLC/rhBMP‐2. In real‐time PCR, the highest gene expression level was observed for Runx2 in hPDLC/harmine at all time points. The level of CEMP‐1 in hPDLC/harmine was higher at 7 days than hPDLCs alone. Thicker band of Runx2 in hPDLC/harmine was observed than in hPDLC/rhBMP‐2 at 7 days by Western blotting. The band for CEMP‐1 in hPDLC/harmine was thicker than hPDLCs alone at both 7 and 14 days. In ectopic transplantation, hPDLCs with harmine showed a comparable amount of mineralized tissue formation compared to rhBMP‐2. hPDLCs with harmine or rhBMP‐2 formed both bone and cementum‐like tissue with Sharpey's fiber‐like collagen insertion.ConclusionHarmine can be a potential candidate for promoting hPDLCs‐induced tissue regeneration.