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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

30卷

期数:

2024年02期

页码:

144-151

栏目:

基础医学

出版日期:

2024-03-20

文章信息/Info

Title:

Mechanical stimulation promotes lipolysis and osteogenesis in osteoporosis mice via the PI3K/Akt pathway

文章编号:

1006-8147（2024）02-0144-08

作者:

吴 秋; 李心乐; 张 平

（天津医科大学基础医学院人体解剖与组织胚胎学系，天津300070）

Author(s):

WU Qiu; LI Xinle; ZHANG Ping

（Department of Anatomy and Histology，School of Basic Medical Sciences，Tianjin Medical University，Tianjin 300070，China）

关键词:

力学刺激; 脂解; 脂肪细胞; 成骨细胞; 骨形成

Keywords:

mechanical stimulation;  lipolysis;  adipocytes;  osteoblasts;  bone formation

分类号:

R684.3

DOI:

10.20135/j.issn.1006-8147.2024.02.0144

文献标志码:

A

摘要:

目的：探究力学刺激对骨质疏松小鼠脂解和成骨的调节作用。方法：45只雌性C57BL/6小鼠，使用随机数字表法分为假手术组、造模组和力学刺激组，每组15只。在小鼠卵巢去势造模2周后，进行为期2周的膝关节力学刺激（1 N，5 Hz，6 min/d）治疗，治疗结束后处死动物。通过HE染色和MacNeal′s染色观察股骨的组织病理改变；油红O染色检测成脂分化；ALP染色检测成骨细胞分化；茜素红S染色检测成骨细胞矿化；细胞免疫荧光和Western印迹检测相关蛋白的表达变化。结果：HE染色和油红O染色结果显示，与造模组相比，力学刺激组抑制骨质疏松小鼠脂肪细胞的数量、周长和面积增多（t=4.544、13.042、6.243，均P<0.01）并抑制成脂分化（t=11.283，P<0.001）；HE染色和MacNeal′s染色结果显示，与造模组相比，力学刺激组促进骨质疏松小鼠骨生成（t=-7.104、-9.701，均P<0.01）；ALP染色和茜素红S染色结果显示，与造模组相比，力学刺激组促进骨质疏松小鼠成骨细胞分化和矿化（t=-2.807，P<0.05）；细胞免疫荧光结果显示，与造模组相比，力学刺激组促进骨质疏松小鼠PI3K/Akt磷酸化和RUNX2表达（t=-4.715、-2.423、-3.873，均P<0.05）；Western印迹分析结果表明，与造模组相比，力学刺激组促进PI3K/Akt通路磷酸化（t=-7.751、-6.048，均P<0.01），使脂解相关蛋白p-HSL、ATGL和成骨相关蛋白RUNX2、ALP的表达升高（t=-1.677、-7.59、-14.702、-4.504，均P<0.05）。结论：力学刺激通过促进PI3K/Akt磷酸化改善骨质疏松小鼠脂解功能和骨生成，有效缓解由卵巢去势引起的脂肪增多和骨量降低。

Abstract:

Objective：To explore the effect of mechanical stimulation on lipolysis and osteogenesis in osteoporosis mice. Methods：Forty-five female C57BL/6 mice were stochastically separated into sham operation group，modeling group and mechanical stimulation group using random number table method，with 15 mice in each group. After 2 weeks of ovarian castration modeling，knee joint mechanical stimulation（1 N，5 Hz，6 min/d） was performed for 2 weeks，and the animals were euthanized after treatment. The histopathologic changes of femur were observed by HE staining and MacNeal′s staining. Lipid differentiation was detected by oil red O staining. Osteoblast differentiation was detected by ALP staining. Mineralization of osteoblasts was detected by alizarin red S staining. The level of relative protein was detected by cellular immunofluorescence and Western blotting. Results：The results of HE staining and oil red O staining showed that compared with the modeling group，the mechanical stimulation group inhibited the increase of adipocyte quantity，perimeter and area（t=4.544，13.042，6.243，all P<0.01） and inhibit lipid differentiation（t=11.283，P<0.001） in osteoporosis mice. The results of HE staining and MacNeal′s staining showed that compared with the model group，the mechanical stimulation group promoted bone formation in osteoporosis mice（t=-7.104，-9.701，both P<0.01）. ALP staining and alizarin red S staining showed that mechanical stimulation promoted the differentiation and mineralization of osteoblasts in mice with osteoporosis，compared with the modeling group（t=-2.807，P<0.05）. Cellular immunofluorescence results showed that compared with the modeling group，the mechanical stimulation group promoted PI3K/Akt phosphorylation and RUNX2 expression in osteoporosis mice（t=-4.715，t=-2.423，-3.873，all P<0.05）. Western blotting analysis showed that compared with the modeling group，the mechanical stimulation group promoted the phosphorylation of PI3K/Akt pathway（t=-7.751，-6.048，both P<0.01），and increased the expression of lipolysis related proteins p-HSL，ATGL and osteo-genic related proteins RUNX2，ALP（t= -1.677，-7.59，-14.702，-4.504，all P<0.01）. Conclusion：Mechanical stimulation improves the lipolysis function and osteogenesis in osteoporosis mice by promoting the phosphorylation of PI3K/Akt，and effectively alleviates the increase of adiposity and low bone mass caused by ovariectomy.

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备注/Memo

备注/Memo:

基金项目 国家自然科学基金资助项目（81772405）
作者简介 吴秋（1999-），女，硕士在读，研究方向：力学刺激调控骨质疏松脂解的机制研究；通信作者：张平，E-mail：pizhang2008@163.com。

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更新日期/Last Update: 2024-03-20