The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice
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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2015-01-01
|
| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/8/1/93 |
| _version_ | 1818132548193091584 |
|---|---|
| author | Esther Wehrle Astrid Liedert Aline Heilmann Tim Wehner Ronny Bindl Lena Fischer Melanie Haffner-Luntzer Franz Jakob Thorsten Schinke Michael Amling Anita Ignatius |
| author_facet | Esther Wehrle Astrid Liedert Aline Heilmann Tim Wehner Ronny Bindl Lena Fischer Melanie Haffner-Luntzer Franz Jakob Thorsten Schinke Michael Amling Anita Ignatius |
| author_sort | Esther Wehrle |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T08:38:35Z |
| format | Article |
| id | doaj.art-fb30b52c1fc14355a952e84ac998a367 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-11T08:38:35Z |
| publishDate | 2015-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-fb30b52c1fc14355a952e84ac998a3672022-12-22T01:14:19ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112015-01-01819310410.1242/dmm.018622018622The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in miceEsther WehrleAstrid LiedertAline HeilmannTim WehnerRonny BindlLena FischerMelanie Haffner-LuntzerFranz JakobThorsten SchinkeMichael AmlingAnita IgnatiusFracture 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.http://dmm.biologists.org/content/8/1/93Whole-body vibrationLMHFVFracture healingOestrogen receptor signallingWnt signalling |
| spellingShingle | Esther Wehrle Astrid Liedert Aline Heilmann Tim Wehner Ronny Bindl Lena Fischer Melanie Haffner-Luntzer Franz Jakob Thorsten Schinke Michael Amling Anita Ignatius The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice Disease Models & Mechanisms Whole-body vibration LMHFV Fracture healing Oestrogen receptor signalling Wnt signalling |
| title | The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice |
| title_full | The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice |
| title_fullStr | The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice |
| title_full_unstemmed | The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice |
| title_short | The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice |
| title_sort | impact of low magnitude high frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice |
| topic | Whole-body vibration LMHFV Fracture healing Oestrogen receptor signalling Wnt signalling |
| url | http://dmm.biologists.org/content/8/1/93 |
| work_keys_str_mv | AT estherwehrle theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT astridliedert theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT alineheilmann theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT timwehner theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT ronnybindl theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT lenafischer theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT melaniehaffnerluntzer theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT franzjakob theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT thorstenschinke theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT michaelamling theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT anitaignatius theimpactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT estherwehrle impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT astridliedert impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT alineheilmann impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT timwehner impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT ronnybindl impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT lenafischer impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT melaniehaffnerluntzer impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT franzjakob impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT thorstenschinke impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT michaelamling impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice AT anitaignatius impactoflowmagnitudehighfrequencyvibrationonfracturehealingisprofoundlyinfluencedbytheoestrogenstatusinmice |