Abstract: Objective To investigate the effect of mechanical loading on bone loss in obese mice induced by high fat diet. Methods Forty-five female C57BL/6 mice were randomly sorted into three groups: normal control group fed with a standard chow diet (Sham group), high-fat diet group (HF group) and high-fat diet with loading group (HF+L group). There were fifteen mice in each group. After HF group and HF + L group were fed with high-fat diet for 4 weeks, HF+L group was received knee loading for the following 4 weeks (loading condition was 1 N, 10 Hz, 3 min/d, continuous loading for 5 days per week). After the treatment, the changes of body mass index (BMI), total body fat content and bone mineral density of femurs were measured in three groups. HE staining and MacNeal's staining were used to observe the pathological changes of the femur. Western blot assay was used to detect the expressions of osteogenesis-related proteins alkaline phosphatase (ALP),Runt-related transcription factor 2 (RUNX2)] and adipogenesis-related proteins proteasome proliferator-activated receptor γ (PPARγ), CCAAT / enhancer-binding protein α (C/EBPα). Results Compared with the Sham group, the body fat content and BMI were significantly increased in the HF group, and the changes of bone mineral density and bone mineral content were significantly decreased in the HF group. Trabecular bone area ratio was significantly reduced in the HF group, and the accumulation of bone marrow fat cells was significantly increased in the HF group. After mechanical loading treatment, the bone density and trabecular bone area ratio were significantly higher in the HF + L group than those in the HF group, and the number and area ratio of adipocytes were significantly lower than those in the HF group (P＜0.05). Western blot analysis showed that mechanical loading improved the low expressions of ALP and RUNX2 in HF + L group, which were significantly higher than those of HF group, while the C/EBPα and PPARγ were significantly decreased (P＜0.05). Conclusion Mechanical loading can effectively restore low bone mineral density and low bone mass caused by obesity. Its therapeutic effect improves obesity-induced bone loss by promoting osteoblast differentiation and inhibiting adipogenesis.

Key words: mechanical loading, obesity, bone loss, osteoblasts, adipocytes