title: The influence of biodegradable magnesium alloys on the osteogenic differentiation of human mesenchymal stem cells.
abstract: The postdegradation effect of pure Mg, Mg-1Y, Mg-5Al, and Mg-2Ca alloys on the differentiation, proliferation and gene expression of human mesenchymal stem cells (hMSCs) was investigated. It was revealed that that Mg(2+) ions result in an increase in cell proliferation. However, we observed a maximum concentration (approximately 8.0 × 10(-4) M) that was favourable to ATP production, above which ATP production began to decrease. In contrast to proliferation, no maximum concentration for osteogenic differentiation was observed, with increasing concentration of Mg(2+) ions resulting in an increase in osteogenic differentiation across the entire tested range. Interestingly, the Mg-2Ca alloy had minimal effect on osteogenic differentiation, with Mg-1Y and pure Mg having a superior effect on the proliferation and differentiation of hMSCs. This was also observed from gene expression data, where these alloys upregulated TGFβ-1, SMAD4, FGF-2, FGF-10, and BMP-2, while SOX-2, SOX-9, and TNF-α were downregulated. Increased expression of TGFβ-1, SMAD4, BMPs, and COLIA1 protein provided further evidence to support osteogenic differentiation and that the influence of the alloying extracts on differentiation may be via the SMAD signaling pathway.
authors.affiliation: The Medical School, The Australian National University, Acton, ACT 0200, Australia; John Curtin School of Medical Research, The Australian National University, Acton, ACT 0200, Australia.
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Li
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Kirkland
authors.forename: John
authors.initials: J
authors.lastname: Truong
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Paul N
authors.initials: PN
authors.lastname: Smith
authors.forename: Nick
authors.initials: N
authors.lastname: Birbilis
authors.forename: David R
authors.initials: DR
authors.lastname: Nisbet
mesh_terms: D020341:Absorbable Implants; D000497:Alloys / Q000737:chemistry / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000096:biosynthesis; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008274:Magnesium / Q000737:chemistry / Q000494:pharmacology; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000497:Alloys; D000943:Antigens, Differentiation; D018786:Bone Substitutes; D008274:Magnesium
keywords: corrosion; human mesenchymal stem cells; implant; magnesium; osteoblast