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Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: an in vitro study
Authors
B Mollon
Bas J Punt
+70 more
C Neidlinger-Wilke
CA Bassett
CF Lai
CF Martino
CM Yang
CT Brighton
CT Rubin
D Kingsley
E Farrell
EW Mandl
F Tabrah
FA Peverali
G Schmidmaier
G Xiao
GS Stein
H Chiba
H Jahr
H Wiesmann
Harrie Weinans
HM Ryoo
Holger Jahr
J Rubin
Jan AN Verhaar
JD Heckman
JH Jansen
JH Jansen
Johannes PTM van Leeuwen
Justus HW Jansen
K Heermeier
K Nie
KF Taylor
KL Grace
L Obert
LA Norton
LY Sun
M De Mattei
M Eijken
M Eijken
M Nagai
MP Bostrom
MT Tsai
N Inoue
N Selvamurugan
NK Kanakaris
OH Lowry
Olav P van der Jagt
OM Tepper
P Diniz
P Diniz
R Gruber
RA Luben
RH Das
RJ Fitzsimmons
RJ Fitzsimmons
RK Aaron
RK Jaiswal
S Khosla
S Matsunaga
SM Tanaka
T Bodamyali
T Kitaori
T Nikolova
TM Skerry
U Karsten
V Sollazzo
WH Chang
XL Griffin
Z Schwartz
Z Schwartz
Z Wang
Publication date
1 January 2010
Publisher
BioMed Central
Doi
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on
PubMed
Abstract
Background: Although pulsed electromagnetic field (PEMF) stimulation may be clinically beneficial during fracture healing and for a wide range of bone disorders, there is still debate on its working mechanism. Mesenchymal stem cells are likely mediators facilitating the observed clinical effects of PEMF. Here, we performed in vitro experiments to investigate the effect of PEMF stimulation on human bone marrow-derived stromal cell (BMSC) metabolism and, specifically, whether PEMF can stimulate their osteogenic differentiation. Methods: BMSCs derived from four different donors were cultured in osteogenic medium, with the PEMF treated group being continuously exposed to a 15 Hz, 1 Gauss EM field, consisting of 5-millisecond bursts with 5-microsecond pulses. On culture day 1, 5, 9, and 14, cells were collected for biochemical analysis (DNA amount, alkaline phosphatase activity, calcium deposition), expression of various osteoblast-relevant genes and activation of extracellular signal-regulated kinase (ERK) signaling. Differences between treated and control groups were analyzed using the Wilcoxon signed rank test, and considered significant when p < 0.05. Results: Biochemical analysis revealed significant, differentiation stage-dependent, PEMF-induced differences: PEMF increased mineralization at day 9 and 14, without altering alkaline phosphatase activity. Cell proliferation, as measured by DNA amounts, was not affected by PEMF until day 14. Here, DNA content stagnated in PEMF treated group, resulting in less DNA compared to control. Quantitative RT-PCR revealed that during early culture, up to day 9, PEMF treatment increased mRNA levels of bone morphogenetic protein 2, transforming growth factor-beta 1, osteoprotegerin, matrix metalloproteinase-1 and-3, osteocalcin, and bone sialoprotein. In contrast, receptor activator of NF-B ligand expression was primarily stimulated on day 14. ERK1/2 phosphorylation was not affected by PEMF stimulation. Conclusions: PEMF exposure of differentiating human BMSCs enhanced mineralization and seemed to induce differentiation at the expense of proliferation. The osteogenic stimulus of PEMF was confirmed by the up-regulation of several osteogenic marker genes in the PEMF treated group, which preceded the deposition of mineral itself. These findings indicate that PEMF can directly stimulate osteoprogenitor cells towards osteogenic differentiation. This supports the theory that PEMF treatment may recruit these cells to facilitate an osteogenic response in vivo. © 2010 Jansen et al; licensee BioMed Central Ltd
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info:doi/10.1186%2F1471-2474-1...
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