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运动通过上调2型糖尿病小鼠的Wnt3a/β-连环蛋白信号通路来改善骨形成。

Exercise improves bone formation by upregulating the Wnt3a/β-catenin signalling pathway in type 2 diabetic mice.

作者信息

Chen Xianghe, Yang Kang, Sun Peng, Zhao Renqing, Liu Bo, Lu Pengcheng

机构信息

College of Physical Education, Yangzhou University, Yangzhou, 225127, Jiangsu, China.

Rehabilitation Medicine Department, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, Jiangsu, China.

出版信息

Diabetol Metab Syndr. 2021 Oct 23;13(1):116. doi: 10.1186/s13098-021-00732-6.

Abstract

BACKGROUND

The bone formation ability of type 2 diabetes is inhibited, and exercise can effectively improve the bone formation of T2DM. However, whether exercise can mediate the Wnt3a/β-catenin pathway to improve the mechanism of bone formation and metabolism still needs further research.

METHODS

A T2DM mouse model was established by a high-fat diet and STZ injection, and the mice were trained with swimming and downhill running exercise. Alizarin red staining is used to observe the changes of the left femoral trabecular bone; micro-CT is used to analyze the trabecular and cortical BMD, BV/TV, BS/BV, BS/TV, Tb.Th, Tb.Sp; the ALP staining of skull was used to observe the changes in ALP activity of bone tissues at the skull herringbone sutures; ALP staining was performed to observe the changes in the number of OBs and ALP activity produced by differentiation; Quantitative PCR was used to detect mRNA expression; Western blot was used to detect protein expression levels.

RESULTS

When the Wnt3a/β-catenin pathway in the bones of T2DM mice was inhibited, the bone formation ability of the mice was significantly reduced, resulting in the degradation of the bone tissue morphology and structure. Swimming caused the significant increase in body weight and Runx2 mRNA expression, while downhill running could significantly decrease the body weight of the mice, 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.

CONCLUSIONS

Bone formation is inhibited in T2DM mice, leading to osteoporosis. Downhill running activates the Wnt3a/β-catenin pathway in the bones of T2DM mice, promotes OB differentiation and osteogenic capacity, enhances bone formation metabolism, and improves the bone morphological structure.

摘要

背景

2型糖尿病的骨形成能力受到抑制,运动可有效改善2型糖尿病患者的骨形成。然而,运动是否能通过介导Wnt3a/β-连环蛋白通路来改善骨形成和代谢机制仍需进一步研究。

方法

通过高脂饮食和注射链脲佐菌素建立2型糖尿病小鼠模型,并对小鼠进行游泳和下坡跑运动训练。采用茜素红染色观察左股骨小梁骨的变化;用微型计算机断层扫描分析小梁和皮质骨密度、骨体积分数、骨表面积与骨体积比、骨表面积与组织体积比、骨小梁厚度、骨小梁间距;对头骨进行碱性磷酸酶染色观察颅骨人字缝处骨组织碱性磷酸酶活性的变化;进行碱性磷酸酶染色观察成骨细胞数量及分化产生的碱性磷酸酶活性变化;采用定量聚合酶链反应检测信使核糖核酸表达;用蛋白质免疫印迹法检测蛋白质表达水平。

结果

当2型糖尿病小鼠骨骼中的Wnt3a/β-连环蛋白通路受到抑制时,小鼠的骨形成能力显著降低,导致骨组织形态和结构退化。游泳使体重和Runx2信使核糖核酸表达显著增加,而下坡跑可使小鼠体重显著降低,同时通过激活Wnt3a/β-连环蛋白通路,胫骨长度、湿重、股骨远端小梁形态结构及骨组织形态计量学指标均得到显著改善。

结论

2型糖尿病小鼠骨形成受到抑制,导致骨质疏松。下坡跑激活2型糖尿病小鼠骨骼中的Wnt3a/β-连环蛋白通路,促进成骨细胞分化和骨生成能力,增强骨形成代谢,改善骨形态结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a947/8542289/73fad001615f/13098_2021_732_Fig1_HTML.jpg

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