酪氨酸磷酸酶SHP2通过激活ERK/cyclin D1信号通路促进间充质干细胞增殖和缓解骨质疏松  

Tyrosine phosphatase SHP2 promotes mesenchymal stem cells proliferation and alleviates osteoporosis through activation of the ERK/cyclin D1 signaling pathway

作　　者：张惠艳 刘斯文 李红岩[1] 代荣琴[1] 刘颖[2] Zhang Huiyan;Liu Siwen;Li Hongyan;Dai Rongqin;Liu Ying(Department of Medical Technology,Cangzhou Medical College,Cangzhou 061000,China;Science and Technology Department,Cangzhou Medical College,Cangzhou 061000,China)

机构地区：[1]沧州医学高等专科学校医学技术系,沧州061000 [2]沧州医学高等专科学校科技处,沧州061000

出　　处：《解剖学杂志》2025年第1期17-22,共6页Chinese Journal of Anatomy

摘　　要：目的:探究间充质干细胞(MSCs)中酪氨酸磷酸酶SHP2对骨质疏松的影响。方法:将40只小鼠均分为假手术组、骨质疏松模型(Model)组、Model+MSCs组和Model+MSCs+SHP2 shRNA组;用双能X线吸收仪检测小鼠骨密度;后剥离小鼠的骨小梁组织,行H-E染色,显微镜下观察,并拍照记录;体外实验,将MSCs分为正常对照(NC)组、骨形态发生蛋白2(BMP-2)组、BMP2+SHP2 shRNA组、BMP2+SHP2 mimic组;进行CCK-8及其单克隆实验;使用免疫印迹检测MSCs中SHP2、ERK、cyclin D1蛋白表达;用免疫印迹检测MSCs中成骨细胞标志物。结果:给予MSCs处理后的骨质疏松小鼠的病情得到明显改善;H-E染色结果显示,假手术组骨小梁显示正常,Model组显示极差,Model+MSCs组其骨小梁显示较Model组明显增多;Model+MSCs+SHP2shRNA组较Model+MSCs组差;CCK-8及单克隆实验结果显示NC组MSCs细胞增殖较少,BMP2刺激组细胞增殖较多,BMP2刺激+SHP2 shRNA组细胞增殖稍少于BMP2刺激组;在加入BMP2后,将MSCs中的SHP2经过shRNA转染处理后可以抑制ERK和cyclinD1及成骨细胞标志物的表达;将MSCs中的SHP2经过mimic转染处理后可以促进ERK和cyclin D1及成骨细胞标志物的表达。结论:MSCs中酪氨酸磷酸酶SHP2可以通过激活ERK/cyclin D1信号通路从而使得MSCs增殖,进而治疗骨质疏松。Objective:To investigate the effect of tyrosine phosphatase SHP2 in mesenchymal stem cells(MSCs)on osteoporosis.Method:Forty mice were evenly divided into sham operation group,osteoporosis model group,osteoporosis model+MSCs group,and osteoporosis model+MSCs+SHP2 shRNA group.A dual energy X-ray absorptiometer was used to detect mouse bone density.The trabecular bone tissue of mice was stripped,stained with Hematoxylin and Eosin(H-E)staining,observed under a microscope,and photographed for records.In vitro experiments,MSCs were divided into NC group,bone morphogenetic protein 2(BMP-2)group,BMP2+SHP2 mimic group,BMP2 stimulation+SHP2 mimic group.CCK-8 and colony formation assays were conducted.Western blotting was used to detect the expression of SHP2,ERK,and cyclin D1 proteins in MSCs cells.Additionally,Western blotting was used to detect osteoblast markers in MSCs.Result:Osteoporotic mice treated with MSCs showed significant improvement in their condition.The H-E staining results showed that the bone trabeculae in the sham group were normal,while those in the Model group were extremely poor.The bone trabeculae in the Model+MSCs group showed a significant increase compared with the Model group.The bone trabeculae in the Model+MSCs+SHP2 shRNA group was worse than those in the Model+MSCs group.CCK-8 and colony formation assays showed that the NC group had less proliferation of MSCs,while the BMP2 stimulation group had more cell proliferation.The BMP2 stimulation+SHP2 shRNA group had slightly less cell proliferation than the BMP2 stimulation group.After adding BMP2,the shRNA transfection of SHP2 in MSCs can inhibit the expression of ERK,cyclin D1 and osteoblast markers.SHP2 in MSCs was transfected with mimic can promote the expression of ERK,cyclin D1,and osteoblast markers.Conclusion:Tyrosine phosphatase SHP2 in MSCs can promote MSCs cell proliferation and treat osteoporosis by activating the ERK/cycli D1 signaling pathway.

关 键 词：间充质干细胞 SHP2 ERK/cyclin D1信号通路 骨质疏松 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]