TY  - JOUR
A1  - Wehrle, Esther
A1  - Liedert, Astrid
A1  - Heilmann, Aline
A1  - Wehner, Tim
A1  - Bindl, Ronny
A1  - Fischer, Lena
A1  - Haffner-Luntzer, Melanie
A1  - Jakob, Franz
A1  - Schinke, Thorsten
A1  - Amling, Michael
A1  - Ignatius, Anita
T1  - The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice
JF  - Disease Models & Mechanisms
N2  - Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 g peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (mu CT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (-81%) and bone formation (-80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+ 1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ER alpha in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERa might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.
KW  - level mechanical vibrations
KW  - ovariectomized rats
KW  - bone formation
KW  - LMHFV
KW  - whole body vibration
KW  - receptor beta
KW  - replacement therapy
KW  - osteoblastic cells
KW  - early stage
KW  - alpha
KW  - Wnt
KW  - fracture healing
KW  - oestrogen receptor signalling
KW  - Wnt signalling
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144700
VL  - 8
ER  - 
TY  - JOUR
A1  - Wehrle, Esther
A1  - Liedert, Astrid
A1  - Heilmann, Aline
A1  - Wehner, Tim
A1  - Bindl, Ronny
A1  - Fischer, Lena
A1  - Haffner-Luntzer, Melanie
A1  - Jakob, Franz
A1  - Schinke, Thorsten
A1  - Amling, Michael
A1  - Ignatius, Anita
T1  - The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice
JF  - Disease Models & Mechanisms
N2  - Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 G: peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (-81%) and bone formation (-80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.
KW  - fracture healing
KW  - LMHFV
KW  - oestrogen receptor signalling
KW  - whole-body vibration
KW  - Wnt-signalling
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121109
VL  - 8
ER  -