Human Mesenchymal Stem Cells-Derived Exosome Mimetic Vesicles Regulation of the MAPK Pathway and ROS Levels Inhibits Glucocorticoid-Induced Apoptosis in Osteoblasts

作者全名："Lu, Hongxu; Zhang, Zhaoxia; Wang, Zhaoying; Wang, Jinkui; Mi, Tao; Jin, Liming; Wu, Xin; Luo, Junyi; Liu, Yimeng; Liu, Junhong; Cai, Wenquan; Guo, Peng; He, Dawei"

作者地址："[Lu, Hongxu; Zhang, Zhaoxia; Wang, Zhaoying; Wang, Jinkui; Mi, Tao; Jin, Liming; Wu, Xin; Luo, Junyi; Liu, Yimeng; Liu, Junhong; Cai, Wenquan; Guo, Peng; He, Dawei] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China; [Lu, Hongxu; Zhang, Zhaoxia; Wang, Zhaoying; Wang, Jinkui; Mi, Tao; Jin, Liming; Wu, Xin; Luo, Junyi; Liu, Yimeng; Liu, Junhong; Cai, Wenquan; Guo, Peng; He, Dawei] Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing 400014, Peoples R China; [Lu, Hongxu; Zhang, Zhaoxia; Wang, Zhaoying; Wang, Jinkui; Mi, Tao; Jin, Liming; Wu, Xin; Luo, Junyi; Liu, Yimeng; Liu, Junhong; Cai, Wenquan; Guo, Peng; He, Dawei] Natl Clin Res Ctr Child Hlth & Disorders, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China; [Lu, Hongxu; Zhang, Zhaoxia; Wang, Zhaoying; Wang, Jinkui; Mi, Tao; Jin, Liming; Wu, Xin; Luo, Junyi; Liu, Yimeng; Liu, Junhong; Cai, Wenquan; Guo, Peng; He, Dawei] Minist Educ, Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China; [Lu, Hongxu; Cai, Wenquan] Chongqing Med Univ, Dept Orthopaed, Childrens Hosp, Chongqing, Peoples R China; [Guo, Peng] Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou 310022, Zhejiang, Peoples R China"

通信作者："He, DW (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China.; He, DW (通讯作者)，Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing 400014, Peoples R China.; He, DW (通讯作者)，Natl Clin Res Ctr Child Hlth & Disorders, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China.; He, DW (通讯作者)，Minist Educ, Key Lab Child Dev & Disorders, Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China."

来源：STEM CELLS INTERNATIONAL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001074026500002

JCR分区：Q2

影响因子：3.8

年份：2023

卷号：2023

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Background. Long-term extensive use of glucocorticoids will lead to hormonal necrosis of the femoral head, and osteoblasts play an important role in the prevention of osteonecrosis. However, there is no complete cure for necrosis of the femoral head. Mesenchymal stem cell- (MSCs-) derived exosomes are widely used for the repair of various tissue lesions. Therefore, the aim of this study was to investigate the mechanism of dexamethasone- (DEX-) induced osteoblast apoptosis and the therapeutic effect of human umbilical cord MSC- (hucMSC-) derived exosome mimetic vesicles (EMVs) on osteoblast-induced apoptosis by DEX. Methods. The viability and apoptosis of primary MC3T3-E1 cells were determined by the Cell Counting Kit-8 (CCK-8), FITC-Annexin V/PI staining and immunoblot. The intracellular levels of reactive oxygen species (ROS) after DEX treatment were measured by 2 & PRIME;, 7 & PRIME; -dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In this study, hucMSC-EMVs and N-acetyl-l-cysteine (NAC) were used as therapeutic measures. The expression of B-cell lymphoma 2-associated X, Bcl 2, HO-1, and nuclear factor erythroid-derived 2-like 2 and MAPK- signaling pathway in osteogenic cell MC3T3-E1 cells treated with Dex was analyzed by the immunoblotting. Results. DEX significantly induced osteoblasts MC3T3-E1 apoptosis and ROS accumulation. MAPK-signaling pathway was activated in MC3T3-E1 after DEX treatment. hucMSC-EMVs intervention significantly downregulated DEX-induced MAPK-signaling pathway activation and ROS accumulation. In addition, hucMSC-EMVs can reduce the apoptosis levels in osteoblast MC3T3-E1 cells induced by DEX. Conclusions. Our study confirmed that hucMSC-EMVs regulates MAPK-signaling pathway and ROS levels to inhibit DEX-induced osteoblast apoptosis."

基金机构：This study was supported by Chongqing Talent Program "lump sum project" (cstc2021ycjh-bgzxm0253) and the Postgraduate Research Innovation Project of Chongqing Medical University (CYB22214). [cstc2021ycjh-bgzxm0253]; Chongqing Talent Program "lump sum project" [CYB22214]; Postgraduate Research Innovation Project of Chongqing Medical University

基金资助正文：This study was supported by Chongqing Talent Program "lump sum project" (cstc2021ycjh-bgzxm0253) and the Postgraduate Research Innovation Project of Chongqing Medical University (CYB22214).