Effect of hypoxia on pluripotent differentiation of periodontal ligament stem cells and related mechanisms

High incidence of periodontal disease occur in plateau regions, as hypoxia may affect biological feature of stem cells including periodontal ligament stem cell (PDLSCs) differentiation. This study thus tested activity of alkaline lipid phosphatase (ALP) and expression level of lipogenesis related gene, in an attempt to illustrate the effect of hypoxia on pluripotent differentiation on PDLSCs, plus an initial investigation of related mechanisms. Isolated PDLSCs were used to study the effect of hypoxia environment on pluripotent differentiation. ELISA was used to test levels of ALP in culture supernatants under different oxygen concentration. Real-time fluorescent quantitative PCR was used to measure mRNA level of PPAR. and LPL. Western blot was employed to quantify expression level of p38/MAPK and MAPK/ERK signal molecules. MPAK inhibitor was further employed to test the role of p38 or ERK in hypoxia-induced pluripotent differentiation potency of PDLSCs. Hypoxia group had significantly higher ALP activity, and lower expression level of PPAR. and LPL (P<0.05 compared to control group). No significant difference existed of total p38 or ERK1/2 of PDLSCs under different oxygen concentrations. Hypoxia group had remarkably elevated expression of phosphorylated p38 and ERK1/2 (P<0.05). p38 inhibitor significantly inhibited ALP activity, and mRNA expression level of PPAR. and LPL, while ERK inhibitor potentiated their expression level. Co-treatment of p38 and ERK inhibitor enhanced levels of these signal molecules (P<0.05). Hypoxia condition inhibits osteogenesis and lipogenesis differentiation potency of PDLSCs, possibly via p38/MAPK and ERK/MAPK signal pathways.