Dataset Information

Protective effects of low-magnitude high-frequency vibration on high glucose-induced osteoblast dysfunction and bone loss in diabetic rats

ABSTRACT:

Objective

Low-magnitude high-frequency vibration (LMHFV) has been reported to be capable of promoting osteoblast proliferation and differentiation. Reduced osteoblast activity and impaired bone formation were related to diabetic bone loss. We investigated the potential protective effects of LMHFV on high-glucose (HG)-induced osteoblasts in this study. In addition, the assessment of LMHFV treatment for bone loss attributed to diabetes was also performed in vivo.

Method

MC3T3-E1 cells induced by HG only or treated with LMHFV were treated in vitro. The experiments performed in this study included the detection of cell proliferation, migration and differentiation, as well as protein expression. Diabetic bone loss induced by streptozotocin (STZ) in rats was established. Combined with bone morphometric, microstructure, biomechanical properties and matrix composition tests, the potential of LMHFV in treating diabetes bone loss was explored.

Results

After the application of LMHFV, the inhibiting effects of HG on the proliferation, migration and differentiation of osteoblasts were alleviated. The GSK3β/β-catenin pathway was involved in the protective effect of LMHFV. Impaired microstructure and biomechanical properties attributed to diabetes were ameliorated by LMHFV treatment. The improvement of femur biomechanical properties might be associated with the alteration of the matrix composition by the LMHFV.

Conclusion

LMHFV exhibited a protective effect on osteoblasts against HG by regulating the proliferation, migration and differentiation of osteoblasts. The function of promoting bone formation and reinforcing bone strength made it possible for LMHFV to alleviate diabetic bone loss.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13018-021-02803-w.

SUBMITTER: Fu Z

PROVIDER: S-EPMC8557505 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project 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 (?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 ? (ER?, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased ?-catenin, suggesting that ER? might mediate these negative effects through inhibition of osteoanabolic Wnt/?-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? in the callus of the vibrated OVX mice, whereas ER? was unaffected, indicating that ER? 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.