中国组织工程研究

中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (2): 231-236.doi: 10.12307/2023.859

• 骨组织构建 bone tissue construction • 上一篇    下一篇

跑台运动对老年大鼠骨质疏松及wnt/β-catenin信号通路的影响

尹林伟1，2，3，黄夏荣1，2，3，屈萌艰1，2，3，杨  璐1，2，3，王金玲1，2，3，贾飞阳1，2，3，廖  阳1，2，3，周  君1，2，3，4   

  1. 南华大学衡阳医学院附属第一医院，1康复医学科，2康复医学中心，3康复医学实验室，湖南省衡阳市  421001；4四川大学华西医院，康复医学四川省重点实验室，四川省成都市  610041
  • 收稿日期:2022-10-09 接受日期:2022-12-15 出版日期:2024-01-18 发布日期:2023-06-30
  • 通讯作者: 周君，博士，主任医师，南华大学衡阳医学院附属第一医院，康复医学科，康复医学中心，康复医学实验室，湖南省衡阳市 421001；四川大学华西医院，康复医学四川省重点实验室，四川省成都市 610041
  • 作者简介:尹林伟，男，1991年生，湖南省衡阳市人，汉族，主管治疗师，主要从事骨、关节疾病康复的基础与临床研究。
  • 基金资助:
    国家自然科学基金面上项目(81973917)，项目负责人：周君；湖南省卫健委重点项目(202103060198)，项目负责人：周君；南华大学校级重点项目子项目(USCKF201902K02)，项目负责人：周君

Effects of treadmill exercise on osteoporosis and wnt/beta-catenin signal pathway in aged rats

Yin Linwei1, 2, 3, Huang Xiarong1, 2, 3, Qu Mengjian1, 2, 3, Yang Lu1, 2, 3, Wang Jinling1, 2, 3, Jia Feiyang1, 2, 3, Liao Yang1, 2, 3, Zhou Jun1, 2, 3, 4   

  1. 1Department of Rehabilitation, 2Rehabilitation Medicine Center, 3Rehabilitation Laboratory, the First Affiliated Hospital of Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China; 4Key Laboratory of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2022-10-09 Accepted:2022-12-15 Online:2024-01-18 Published:2023-06-30
  • Contact: Zhou Jun, MD, Chief physician, Department of Rehabilitation, Rehabilitation Medicine Center, Rehabilitation Laboratory, the First Affiliated Hospital of Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China; Key Laboratory of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • About author:Yin Linwei, Therapist in charge, Department of Rehabilitation, Rehabilitation Medicine Center, Rehabilitation Laboratory, the First Affiliated Hospital of Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
  • Supported by:
    National Natural Science Foundation of China (General Program), No. 81973917 (to ZJ); Hunan Provincial Health Commission Key Project, No. 202103060198 (to ZJ); School-level Key Project of the University of South China, No. USCKF201902K02 (to ZJ)

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摘要：


文题释义：

骨质疏松症：是一种骨量丢失、降低，骨微结构破坏、骨脆性增加的全身性骨疾病。老年人因运动量减少、激素水平改变而成为高危人群。
wnt/β-catenin信号通路：广泛参与正常生理活动过程。在骨代谢过程中，通过激活其核心蛋白β-catenin，上调骨形态发生蛋白2、骨保护素及下调核因子κB受体活化因子配体的表达，进而促进间充质干细胞成骨分化和抑制破骨细胞活性，起到促进骨形成和抑制骨吸收的作用。


背景：运动训练有改善骨质疏松的作用，但其对于老年骨质疏松的作用及机制尚未完全明确。

目的：观察跑台运动对老年大鼠骨质疏松及wnt/β-catenin信号通路的影响。
方法：取16只24月龄雄性SD大鼠，采用随机抽样法分为骨质疏松症组和跑台组，每组8只，以自然衰老复制老年骨质疏松模型，同时跑台组大鼠进行跑台运动干预8周，1次/d，5 d/周；将8只6月龄雄性SD大鼠作为青年组。8周后，采用ELISA法检测各组大鼠血清中骨代谢标志物Ⅰ型胶原交联C末端肽、抗酒石酸酸性磷酸酶、骨钙素、骨特异性碱性磷酸酶水平，双能X射线检测左股骨与L5骨密度，使用骨显微CT行胫骨和L4椎体扫描及骨微结构定量分析，RT-PCR和Western blot检测骨髓中wnt3a、β-catenin、LRP5、DKK1、GSK3β的mRNA和蛋白表达。

结果与结论：①与青年组相比，骨质疏松症组大鼠血清骨特异性碱性磷酸酶及骨钙素水平降低(P < 0.05)，左股骨和L5椎体骨密度降低(P < 0.05)，胫骨和L4椎体骨小梁数量、骨体积、骨体积分数减少(P < 0.05)，骨髓中wnt3a、β-catenin、LRP5 mRNA水平及蛋白表达降低(P < 0.05)；血清抗酒石酸酸性磷酸酶、Ⅰ型胶原交联C末端肽水平升高(P < 0.05)，胫骨和L4椎体骨小梁间隙、结构模型指数升高(P < 0.05)，骨髓中DKK1、GSK3β的mRNA及蛋白表达升高(P < 0.05)；胫骨、L4椎体骨小梁数量减少，结构紊乱、排列稀疏断裂；②与骨质疏松症组相比，跑台组大鼠血清骨特异性碱性磷酸酶、骨钙素水平升高(P < 0.05)，左股骨和L5椎体骨密度升高(P < 0.05)，胫骨骨小梁数量、骨体积、骨体积分数升高(P < 0.05)，骨髓中wnt3a、β-catenin、LRP5 mRNA及蛋白表达升高(P < 0.05)；血清抗酒石酸酸性磷酸酶、Ⅰ型胶原交联C末端肽水平降低，L4椎体骨小梁间隙，胫骨骨小梁间隙、结构模型指数降低，骨髓中DKK1、GSK3β的mRNA水平及蛋白表达降低(P < 0.05)；胫骨、L4椎体骨小梁数量明显增加，排列较规整致密，连成网状；③结果显示，跑台运动可能通过激活wnt/β-catenin信号通路改善老年大鼠骨质疏松。

https://orcid.org/0000-0001-7172-977X(尹林伟)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 跑台运动, wnt/β-catenin信号通路, 骨质疏松, 自然衰老, 老年骨质疏松

Abstract: BACKGROUND: Exercise training can improve osteoporosis, but its effects and mechanisms on senile osteoporosis are not fully understood.
OBJECTIVE: To observe the effect of treadmill exercise on osteoporosis and wnt/β-catenin signal pathway in aged rats. 
METHODS: Sixteen 24-month-old male Sprague-Dawley rats were randomly divided into osteoporosis group (n=8) and treadmill group (n=8) and eight 6-month-old male Sprague-Dawley rats were used as young control group. The model of senile osteoporosis was replicated by natural aging and the rats in the treadmill group were treated with treadmill exercise once a day, 5 days a week, for 8 weeks. Levels of bone metabolic markers such as type I collagen cross-linked C-terminal peptide, tartrate resistant acid phosphatase, osteocalcin and bone specific alkaline phosphatase were detected by ELISA; bone mineral density of the left femur and L5 was measured by dual energy X-ray; bone scanning and bone microstructure quantitative analysis were performed by bone micro-CT; and the mRNA and protein expression levels of wnt3a, β-catenin, LRP5, DKK1 and GSK3β were detected by RT-PCR and western blot, respectively. 
RESULTS AND CONCLUSION: Compared with the young control group, the osteoporosis group showed a reduction in serum bone specific alkaline phosphatase and osteocalcin levels (P < 0.05), bone mineral density of the femur and L5, the number of tibia and L4 bone trabeculae, bone volume, bone volume fraction (P < 0.05), and mRNA and protein expression of wnt3a, β-catenin, and LRP5 in bone marrow tissue (P < 0.05) as well as an increase in serum levels of tartrate resistant acid phosphatase and type I collagen cross-linked C-terminal peptide (P < 0.05), the intertrabecular space between the tibia and L4, structural model index (P < 0.05), and mRNA and protein expression of DKK1 and GSK3 β in bone marrow tissue (P < 0.05). In addition to the reduced number of trabeculae in the tibia and L4 vertebrae, the trabeculae were structurally disturbed and sparsely aligned and fractured. Compared with the osteoporosis group, the treadmill group showed an increase in serum bone specific alkaline phosphatase and osteocalcin levels (P < 0.05), bone mineral density of the femur and L5 (P < 0.05), the number of tibial trabeculae, bone volume, bone volume fraction (P < 0.05), mRNA and protein expression of wnt3a, β-catenin, and LRP5 in bone marrow tissue (P < 0.05) but a reduction in the serum levels of tartrate resistant acid phosphatase and type I collagen cross-linked C-terminal peptide, L4 trabecular space, tibial trabecular space, structural model index, and mRNA and protein expression of DKK1 and GSK3 β in bone marrow tissue (P < 0.05). In addition to the increased number of tibial and L4 trabeculae, the trabeculae were arranged in a regular and dense pattern and were connected to a network. To conclude, treadmill exercise may improve osteoporosis in aged rats by activating the wnt/β-catenin signal pathway.

Key words: treadmill exercise, wnt/β-catenin signal pathway, osteoporosis, natural aging, senile osteoporosis

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