title: The effect of electromagnetic fields on the proliferation and the osteogenic or adipogenic differentiation of mesenchymal stem cells modulated by dexamethasone.
abstract: Although glucocorticoids provide benefits for inflammation or autoimmune disorders, high-dose and long-term use could cause osteonecrosis or osteoporosis as adverse effect for patients. Electromagnetic field (EMF) treatments have been clinically used for many years to promote fracture healing, but whether EMF can attenuate the deleterious effects of glucocorticoids is not clear. In this study, the effects of different concentrations of dexamethasone (DEX) on proliferation and adipogenic or osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were detected and compared, and the effects of EMF treatment (15 Hz, 1 mT, 4 h/day) on 0.1 µM DEX-modulated BMSCs' proliferation and adipogenic or osteogenic differentiation were investigated. Higher concentrations of DEX (0.1 and 1 µM) inhibited proliferation of BMSCs but promoted expression of adipogenic-related genes, increasing the number of lipid droplets. In the early stage of differentiation, DEX restrained expression of RUNX2 and alkaline phosphatase (ALP), but amplified expression of ALP and osteopontin (OPN) in the late stage. EMF treatment of BMSCs influenced by 0.1 µM DEX inhibited the high expression of adipogenic-related genes, stimulated the expression of RUNX2, ALP, OPN, and osteocalcin, and increased the activity of ALP. EMF exposure augmented the expression of p-ERK, which DEX reduced. After using mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway inhibitor, U0126, the effect of EMF was reduced. In conclusion, EMF exposure accelerates BMSCs proliferation, inhibits adipogenic differentiation, and promotes osteogenic differentiation of BMSCs modulated by DEX, and these effects are mediated at least in part by MEK/ERK signaling pathway.
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Song
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhao
authors.forename: Sheng
authors.initials: S
authors.lastname: Wei
authors.forename: Chaoxu
authors.initials: C
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Wenchun
authors.initials: W
authors.lastname: Zhao
authors.forename: Kaixiang
authors.initials: K
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
mesh_terms: D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004574:Electromagnetic Fields; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D066292:Lipid Droplets / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D009570:Nitriles; C113580:U 0126; D003907:Dexamethasone
keywords: ERK1/2; dexamethasone; differentiation; electromagnetic fields; mesenchymal stem cell; proliferation