title: Phosphatidylserine enhances osteogenic differentiation in human mesenchymal stem cells via ERK signal pathways.
abstract: Phosphatidylserine (PS) has been demonstrated to promote bone mineralization. It has also been used in bone repairing biomaterials as a functional molecule. However, the effect of PS on mesenchymal stem cells (MSCs) is not clear. In this study, we determined the effect of PS on the osteogenic differentiation of human MSCs (hMSCs) cultured in growth or osteogenic differentiation medium and the role of the ERK1/2 signaling pathway on PS activity. Cytotoxicity of PS was measured by MTT assay in growth medium for 5 days. Cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity analysis, Alizarin Red S staining and real-time PCR assay. Western blotting and ERK blocking assay were used to examine the role of ERK1/2 signaling pathway on PS activity. The results showed no cytotoxicity for the doses of PS administered. For 21 days, 50-100 μM PS increased ALP expression and mineralization of hMSCs. The expression of the osteogenic gene marker, ALP, osteocalcin (OC), and RUNX2 was enhanced by 50 μM PS treatment at day 14. Phospho-ERK was activated by 50 μM PS at 30 min and 1h in growth medium. In osteogenic medium, 50 μM PS extended phospho-ERK activation by osteogenic induction medium from 30 min to 8 h. U0126, an ERK inhibitor, suppressed the ALP expression induced by PS. Our data indicate that the ERK signal is potentially a mediator in the process of osteogenic differentiation of hMSCs induced by PS. PS, as a functional molecule, has high potential for use in bone repairing biomaterials and bone tissue engineering.
authors.affiliation: College of Materials Science and Engineering, South China University of Technology, Ministry of Education, Guangzhou, Guangdong 510641, China. xucaixia3995@163.com
authors.forename: Caixia
authors.initials: C
authors.lastname: Xu
authors.forename: Zebin
authors.initials: Z
authors.lastname: Zheng
authors.forename: LiMing
authors.initials: L
authors.lastname: Fang
authors.forename: Naru
authors.initials: N
authors.lastname: Zhao
authors.forename: Zihong
authors.initials: Z
authors.lastname: Lin
authors.forename: Tangzhao
authors.initials: T
authors.lastname: Liang
authors.forename: Zhichen
authors.initials: Z
authors.lastname: Zhai
authors.forename: Jiaan
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D009570:Nitriles / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D010718:Phosphatidylserines / Q000494:pharmacology*; D013194:Staining and Labeling
chemical_list: D002070:Butadienes; D009570:Nitriles; D010718:Phosphatidylserines; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase
keywords: Differentiation; Mesenchymal stem cells; Phosphatidylserine; Signal pathway