| Backgroud:As people’s living standards improve, type 2 diabetes mellitus (T2DM) is gradually prevalent. The bone, body’s vital organ, has an important role in the protection, support and endocrine. T2DM, systemic metabolic disease, can make the body resistant to insulin, insulin secretion, and thus make bone resorption greater than bone formation,which result in bone loss, osteoporosis. Reasonable exercise can regulate bone metabolism, increasing bone density and bone mass. The specific mechanism for exercise regulating T2DM bone metabolism is unclear. Bone marrow mesenchymal stem cells (BMSCs) have an important role in T2DM bone metabolism. T2DM can regulate that BMSCs differentiate into osteoblasts, adipocytes by mediating Wnt/β-catenin pathway factor, adipocyte related factors. The study have demonstrated that fat cells increase, resulting in decreased bone mass, osteoporosis. But whether exercise impact on BMSCs differentiation into osteoblasts and adipocytes, which is unclear. Firstly mouse model of type 2 diabetes was constructed, and then they were trained in different ways exercise to explore the effect of different kinds of exercise on T2DM bone metabolism and its mechanism in this article.Objective:The purpose of this study was to investigate the bone metabolism in type 2 diabetic mice as well as comparison about the effect of different kinds of exercise (downhill running and swimming) on the osteogenic and adipogenic differentiation of mesenchymal stem cells in the type 2 diabetic mice. It further explores the impact of exercise and type2 diabetes on bone tissue and its mechanism.Methods:In order to build the model of type 2 diabetes,804-week-old C57BL/6 mice firstly had high fat diet and STZ injections and then were randomly divided into four groups after the success:normal quiet group(ZC), quiet type 2 diabetes group(TC), type 2 diabetes swimming group(TS), type 2 diabetes downhill running group(TD). After eight weeks exercise, they were detected bone density, humerus length, width; gene expression of Wnt/β-catenin pathway and fat-related factor and protein expression; cells staining after mesenchymal stem cells osteogenic and adipogenic differentiation.Results:(1) Compared with the ZC group, the weight of the TC group significantly increased (P<.01).; Compared with the TC group, the weight of the TS group and the TD group was significantly decreased(P<0.01). (2) Compared with the ZC group, the bone mineral density in TC mice cortical and trabecular significantly decreased(P<0.01). Compared with the group TC, the bone mineral density in TD mice trabecular significantly increased (P<0.01); (3)Compared with ZC group, sagittal width in TC mice proximal humerus (P<0.01), the coronal width in TC mice proximal humeru (P<0.05) significantly increased.Compared with the TC group, the length of the humerus in TD mice significantly increased (P<0.01). (4) Compared with ZC group, Wnt3a mRNA expression (P<0.05), LRP5 mRNA expression (P<0.01), DVL mRNA expression (P<0.05), β-catenin mRNA expression (P<0.05), Runx2 mRNA (P<0.05) expression in TC mice significantly decreased, and CEBP/β mRNA(P<0.05) expression PPARy mRNA expression (P<0.05) significantly increased. Compared with TC group, Wnt3a mRNA expression (P<0.05), LRP5 mRNA expression (P<0.05), DVL mRNA expression (P<0.05), β-catenin expression mRNA (P<0.05), Runx2 mRNA expression (P<0.01) in TD group mice significantly increased, and CEBP/β mRNA expression(P<0.05), PPARymRNA expression significantly decreased(P<0.05).(5)Compared with the ZC group, β-catenin protein expression in TC group mice significantly decreased (P<0.05).Compared with the TC group, β-catenin protein expression in the TD group significantly increased (P<0.05).(6) Compared with normal group, the color of ALP staining in TC group after osteogenic differentiation was light and the color in TS group.and TD group was sequentially deepen. Compared with normal group, the number of fat cells after oil red O staining in TC group after osteogenic differentiation was increase.Compared TC group, the number of fat cells in TD group and TS group was sequentially decreased.Conclusions:(1)The bone density significantly decreased in T2DM mice. (2)The adipogenic differentiation and osteogenic differentiation in bone marrow mesenchymal stem cell of T2DM mice imbalance.(3) Downhill running significantly increased bone mineral density. (4) Downhill running can increase the cytokines mRNA expression in Wnt/β-catenin signaling pathway,down-regulate the mRNA expression of fat-related factors, inhibit fat cell formation and promote bone marrow mesenchymal stem cells into bone formation. |
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