Exercise Improves Bone Formation by Upregulating the Wnt3a/β-catenin Signalling Pathway in Type 2 Diabetic Mice

Abstract

Bone formation in type 2 diabetes mellitus (T2DM) is inhibited by decreased bone formation capacity. Exercise can significantly improve bone metabolism; however, the effect and mechanism of exercise on bone formation in T2DM is not known. In this study, we used the method of a high-fat diet and injecting STZ to build a T2DM mouse model, and the mice were treated with swimming and downhill running for 8 weeks. Their body weights were obtained using an electronic scale. Their bone length and wet weights were measured by Vernier callipers and an electronic balance. The bone microstructure of the distal femur was analysed by Alizarin red staining of paraffin sections and micro-CT. An ALP dye was used to detect the changes in ALP activity in the mouse skull and osteoblasts. Alizarin red staining was applied to stain the osteoblasts produced by BMSCs. The mRNA expression of related factors were detected by RT-PCR. Our results showed that the body weights of T2DM mice were significantly increased by exercise. When the Wnt3a/β-catenin pathway in the bones of T2DM mice is inhibited, their bone formation ability is significantly reduced, resulting in the degradation of the bone tissue morphology and structure. Except for the significant increase in body weight and Runx2 mRNA expression, swimming had no significant effect on bone formation-related indicators in T2DM mice. However, downhill running could significantly increase their body weight, while the tibia length, wet weight, and the trabecular morphological structure of the distal femur and the indexes of bone histomorphology were significantly improved by activating the Wnt3a/β-catenin pathway. Compared with swimming, downhill running can activate the Wnt pathway to improve bone formation ability, thereby improving bone histomorphology. These findings suggest that exercise promotes OB differentiation, osteogenic capacity and enhances bone formation metabolism by regulating Wnt3a/β-catenin signalling in T2DM mice.

Nano artificial periosteum PLGA/MgO/Quercetin accelerates repair of bone defects through promoting osteogenic − angiogenic coupling effect via Wnt/ β-catenin pathway

“…Wnt/β-Catenin signaling pathway is a canonical osteogenic pathway. An up regulation of Wnt3a could stimulate β-catenin and increasing osteogenesis [ 49 ]. Both Que and Mg 2+ could help bone defect repair by activating Wnt/β-catenin signaling pathway [ 22 , 48 , 50 ].…”

Regulation of bone health through physical exercise: Mechanisms and types

“…Subsequently, osteoblasts differentiation, osteogenic capacity, and bone morphological structure are enhanced. In a word, downhill running reverses osteoporosis by activating Wnt signaling in osteoblasts (51).…”