Effect Of Hypoxia On The Self-renew And Multipotency Of Periodontal Ligament Stem Cells(PDLSCs)

Objective: The incidence of periodontal disease in the plateau population was much higher than people in plain environment.This might be due to the inefficiency of periodontal ligament stem cells?PDLSCs?under hypoxia condition.Thus,this study would investigate the functions of hypoxia on maintaining the stemness of PDLSCs,which including self-renewal and mutipotency.And we further explored the underlying mechanisms.Materials and Methods: The PDLSCs were generated from human molars using limiting solution technique.The PDLS cells were incubated in hypoxia condition?5% O₂?and normal oxygen condition?20%?.The sphere formation ability was compared by culturing cells in serum free culture medium.The proliferation alility of PDLSCs was measured using MTT assay.The multipotency of PDLSCs under hypoxia was investigated through detecting the osteogenic potential and adipogenic potential.Then,we performed western blotting technology to study the activities of p38/MAPK and ERK/MAPK signaling under hypoxia.Finally,specific MAPK inhibitors were applied to investigate the involvement of p38/MAPK and ERK/MAPK in maintaining the stemness of PDLSCs under hypoxia.Results: The PDLSCs could maintain its stem cell marker expression under hypoxia condition,which including.Hypoxia could promote the sphere formation ability and proliferation capability of PDLSCs.The activity of alkaline phosphatase,as a representative maker for the osteogenic differentiation,was statistically significant higher in the hypoxia group than the control normal oxygen group?P < 0.001?.Both p38/MAPK and ERK1/2 were phosphorylated under hypoxia condition.MAPK inhibitors could inhibit the colony formation and proliferation of PDLSCs,which increased the expression of ALPase,PPAR? and LPL.Conclusion: These results suggested that PDLSCs could maintain the self-renewal ability in hypoxia condition.But hypoxia could inhibit the osteogenic and adipogenic differentiation.And the effect of hypoxia on the stemness of PDLSCs was regulated by p38/MAPK and ERK/MAPK pathways.