Kaempferol promotes the osteogenesis in rBMSCs via mediation of SOX2/ miR-124-3p/PI3K/Akt/mTOR axis

被引:38
作者
Gan, Li [1 ,2 ]
Leng, Yu [3 ]
Min, Jun [1 ]
Luo, Xin-Ming [1 ,2 ]
Wang, Fen [1 ]
Zhao, Jing [1 ,2 ,4 ]
机构
[1] Second Affiliated Hosp Nanchang, Dept Neurol, Nanchang 330006, Jiangxi, Peoples R China
[2] Nanchang Univ, Inst Neurosci, Nanchang 330006, Jiangxi, Peoples R China
[3] First Peoples Hosp Jiujiang City, Dept Emergency, Jiujiang 332000, Jiangxi, Peoples R China
[4] Second Affiliated Hosp Nanchang, Dept Neurol, 1, Minde Rd, Nanchang 330006, Jiangxi, Peoples R China
关键词
Osteoporosis; RBMSCs; Kae; miR-124-3p; SOX2; PI3K; Akt; mTOR; MESENCHYMAL STEM-CELLS; DIFFERENTIATION;
D O I
10.1016/j.ejphar.2022.174954
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: It is reported that the osteogenesis in bone marrow mesenchymal stem cells (BMSCs) can alleviate osteoporosis progression. It has been found that Kae can promote the osteogenesis in BMSCs. However, the mechanism by which Kae mediates the osteogenesis in BMSCs is largely unknown.Methods: RBMSCs were collected from rats. The cytotoxicity of Kae was detected by CCK-8 assay. The osteogenic calcification in rBMSCs was measured by alizarin red staining, and ALP staining was performed to test the ALP activity in rBMSCs. The binding relationship between SOX2 and miR-124-3p was explored by dual luciferase report assay and Chromatin Immunoprecipitation (ChIP). RT-qPCR and western blot were performed to assess mRNA and protein levels, respectively.Results: Kae (10 mu M) significantly increased the calcification, ALP activity, SOX2 level, activated PI3K/Akt/mTOR signaling and inhibited miR-124-3p level in rBMSCs, while knockdown of SOX2 reversed this phenomenon. Meanwhile, SOX2 suppressed the transcription of miR-124-3p, and SOX2 promoted the osteogenic differentiation in rBMSCs via regulation of miR-124-3p. MiR-124-3p could inactivate PI3K/Akt/mTOR to inhibit the osteogenic differentiation.Conclusion: Kae significantly promoted the osteogenesis in rBMSCs via mediation of SOX2/miR-124-3p/PI3K/ Akt/mTOR axis. Thus, our study might shed new lights in exploring new methods against osteoporosis.
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页数:10
相关论文
共 35 条
[1]  
Abdallah B.M., J APPL BIOMED, V19, P159
[2]   Quercetin promotes bone marrow mesenchymal stem cell proliferation and osteogenic differentiation through the H19/miR-625-5p axis to activate the Wnt/β-catenin pathway [J].
Bian, Wei ;
Xiao, Shunqiang ;
Yang, Lei ;
Chen, Jun ;
Deng, Shifang .
BMC COMPLEMENTARY MEDICINE AND THERAPIES, 2021, 21 (01)
[3]   Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells [J].
Castel, Gael ;
Meistermann, Dimitri ;
Bretin, Betty ;
Firmin, Julie ;
Blin, Justine ;
Loubersac, Sophie ;
Bruneau, Alexandre ;
Chevolleau, Simon ;
Kilens, Stephanie ;
Chariau, Caroline ;
Gaignerie, Anne ;
Francheteau, Quentin ;
Kagawa, Harunobu ;
Charpentier, Eric ;
Flippe, Lea ;
Francois--Campion, Valentin ;
Haider, Sandra ;
Dietrich, Bianca ;
Knoefler, Martin ;
Arima, Takahiro ;
Bourdon, Jeremie ;
Rivron, Nicolas ;
Masson, Damien ;
Fournier, Thierry ;
Okae, Hiroaki ;
Freour, Thomas ;
David, Laurent .
CELL REPORTS, 2020, 33 (08)
[4]   CircRNA_28313/miR-195a/CSF1 axis modulates osteoclast differentiation to affect OVX-induced bone absorption in mice [J].
Chen, Xia ;
Ouyang, Zhengxiao ;
Shen, Yi ;
Liu, Bo ;
Zhang, Qiang ;
Wan, Lu ;
Yin, Ziqing ;
Zhu, Wei ;
Li, Shuai ;
Peng, Dan .
RNA BIOLOGY, 2019, 16 (09) :1249-1262
[5]   Activating PIK3CA mutation promotes osteogenesis of bone marrow mesenchymal stem cells in macrodactyly [J].
Cui, Hengqing ;
Han, Gang ;
Sun, Bin ;
Fang, Xia ;
Dai, Xinyi ;
Zhou, Shengbo ;
Mao, Hailei ;
Wang, Bin .
CELL DEATH & DISEASE, 2020, 11 (07)
[6]  
de la Rocha Arlet Maria Acanda, 2020, Arch Clin Biomed Res, V4, P221, DOI [10.26502/acbr.50170100, 10.26502/acbr.50170100]
[7]   Carcinoma-Associated Fibroblasts Promote Growth of Sox2-Expressing Breast Cancer Cells [J].
Dittmer, Angela ;
Dittmer, Jurgen .
CANCERS, 2020, 12 (11) :1-22
[8]   The Effect of hsa-miR-451b Knockdown on Biological Functions of Gastric Cancer Stem-Like Cells [J].
Farahani, Diba Borzabadi ;
Akrami, Hassan ;
Moradi, Behrouz ;
Mehdizadeh, Kiumars ;
Fattahi, Mohammad Reza .
BIOCHEMICAL GENETICS, 2021, 59 (05) :1203-1224
[9]   Glucocorticoids Enhanced Osteoclast Autophagy Through the PI3K/Akt/mTOR Signaling Pathway [J].
Fu, Lingjie ;
Wu, Wen ;
Sun, Xiaojiang ;
Zhang, Pu .
CALCIFIED TISSUE INTERNATIONAL, 2020, 107 (01) :60-71
[10]   MiR-1224-5p Activates Autophagy, Cell Invasion and Inhibits Epithelial-to-Mesenchymal Transition in Osteosarcoma Cells by Directly Targeting PLK1 Through PI3K/AKT/mTOR Signaling Pathway [J].
Jin, Bicheng ;
Jin, Dongfang ;
Zhuo, Zhaozhen ;
Zhang, Bo ;
Chen, Kun .
ONCOTARGETS AND THERAPY, 2020, 13 :11807-11818