Palm Mixed-Carotenes Modulate Viability, Wound Closure and Osteoprotegerin mRNA Expression in Human Periodontal Ligament Stem Cells

Background/Objectives: Periodontitis is characterized by the gradual breakdown of tooth-supporting tissues, including the periodontal ligament and alveolar bone, while current regenerative strategies remain limited. Palm mixed-carotenes (PMC), a natural carotenoid-rich compound with antioxidant and cytoprotective properties, may have potential in periodontal regenerative research. However, its effects on human periodontal ligament stem cells (hPDLSCs) remain underexplored. This study evaluated the effects of PMC on hPDLSC viability, wound closure, and osteogenic- and bone remodeling-related molecular responses. Methods: Primary hPDLSCs were isolated, characterized, and treated with PMC at concentrations ranging from 0 to 100 μg/mL. Cell viability was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, wound closure using a wound-scratch assay, gene expression of osteoprotegerin (OPG), osteopontin (OPN), and osteocalcin (OCN) using real-time polymerase chain reaction (RT-qPCR), and secreted protein levels using enzyme-linked immunosorbent assay (ELISA). Results: PMC showed a biphasic viability response, with 6.25 μg/mL producing the most favorable effect by increasing the cell viability to 111.6% relative to the negative control. This concentration was selected, together with 12.5 μg/mL, for subsequent assays. In the wound-scratch assay, 6.25 μg/mL PMC significantly enhanced wound closure at 48 and 72 h, reaching 75.17% at 72 h compared with 52.69% in the negative control. Gene expression analysis showed that 6.25 μg/mL PMC significantly upregulated OPG mRNA expression compared with the negative control, 12.5 μg/mL PMC, and positive control groups. OPN and OCN showed limited responses, and PMC did not significantly increase secreted OPG or OCN protein levels. Conclusions: Overall, PMC at 6.25 μg/mL demonstrated the most favorable response in hPDLSCs, suggesting its potential as a bioactive candidate for further periodontal regenerative research.