Effect of melatonin on the osteogenic differentiation of periodontal ligament stem cells: in vitro study
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Updated: Jul 2, 2026
Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
Razan Alauti1, Areej Mukhtar2, Razan Alaqeely3
1Specialist in Periodontal Surgery and implant dentistry, Alajaji Dental Clinics, Riyadh, 14262, Saudi Arabia.
Background:
Periodontal regeneration is a viable treatment, but outcomes remain variable. Incorporating stem cells and bioactive agents could enhance regeneration. Human periodontal ligament stem cells (hPDLSCs) display osteogenic potential, and melatonin, a neurohormone, modulates osteoblast differentiation and stimulates osteogenesis in dental stem cells. However, the influence of melatonin dosage on hPDLSC differentiation is poorly understood.This study aims to evaluate the effects of varying melatonin concentrations on periodontal hPDLSC osteogenic differentiation.
Methods:
hPDLSCs were cultured with melatonin at 0, 0.01, 10, 20, 30, 40, 50, 100, and 150 µM; viability (AlamarBlue) and differentiation (immunocytochemistry, ELISA, Alizarin Red) were assessed at 14 and 21 days.
Results:
All melatonin‑treated groups exhibited enhanced hPDLSC viability compared to the control. Cell viability decreased dose‑dependently, with the lowest viability in the 100 µM and 150 µM groups. Notably, 20 µM and 50 µM treatments deviated from this trend, showing significant viability increases. Collagen type I expression and calcium mineralization were observed in all groups, increasing over time, with maximal deposits at 21 days versus 14 days. The 20 µM and 50 µM groups demonstrated a statistically significant rise in mineral deposition after 21 days in osteogenic media.
Conclusion:
Melatonin is biocompatible and dose-dependently stimulates hPDLSC viability. Melatonin concentrations of 20 and 50 µM were most effective for osteogenic differentiation of hPDLSCs. Our results show that melatonin directly accelerated the differentiation of human periodontal stem cells into osteoblasts and might be used as a pharmaceutical to promote bone regeneration.
