Noninvasive up-regulation of angiopoietin-2 and fibroblast growth factor-2 in bone marrow by pulsed electromagnetic field therapy.
BACKGROUND
Pulsed electromagnetic field (PEMF) therapy has been widely used in clinical practice for bone fracture healing. However, the mechanism of its action remains to be elucidated. Our object was to investigate the mechanism by which PEMF accelerates bone fracture healing.


METHODS
We used 20 mice in this study. Ten mice received PEMF for 10 h/day for 1 week via the coils of a PEMF stimulation device (PEMF group), while the remaining 10 mice did not (control group). The femurs were harvested immediately after euthanasia to examine the proteins included in the bone marrow. The proteins examined by Western blotting were growth factors with angiogenetic activities, including tunica interna endothelial cell kinase-2, angiopoietin-1, angiopoietin-2, fibroblast growth factor-2, and vascular endothelial growth factor. The expression levels of angiogenesis-related proteins extracted from the bone marrow of each mouse were compared.


RESULTS
The expression levels of angiopoietin-2 and fibroblast growth factor-2 were significantly higher in the PEMF group than in the control group. This difference suggests that PEMF may induce an angiogenesis-prone environment in the bone marrow. Such angiogenesis acceleration represents one possible mechanism for the acceleration of bone fracture healing by PEMF. There were no significant differences between the two groups for the expression levels of tunica interna endothelial cell kinase-2, angiopoietin-1, and vascular endothelial growth factor. The lack of increase in tunica interna endothelial cell kinase-2 expression may indicate that PEMF does not unnecessarily increase blood vessels in normal bone marrow. The lack of an increase in the expression level of vascular endothelial growth factor suggests that PEMF does not have invasive effects including the induction of hypoxic conditions and inflammation on the bone marrow.


CONCLUSIONS
The angiogenesis-promoting function of PEMF may contribute to its mechanism to noninvasively accelerate bone fracture healing.
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-chou, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Tsuyoshi
T
Goto
Mikihiro
M
Fujioka
Masashi
M
Ishida
Masaaki
M
Kuribayashi
Keiichiro
K
Ueshima
Toshikazu
T
Kubo
D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D005269:Femur; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D017102:Fracture Healing; D055909:Magnetic Field Therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018919:Neovascularization, Physiologic; D042787:Receptor, TIE-2 / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D042787:Receptor, TIE-2