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

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

doi:10.1155/2023/5537610

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

Stem Cells Int. 2023 Sep 20:2023:5537610. doi: 10.1155/2023/5537610. eCollection 2023.

Authors

Hongxu Lu^{1

2

3

4

5}, Zhaoxia Zhang^{1

2

3

4}, Zhaoying Wang^{1

2

3

4}, Jinkui Wang^{1

2

3

4}, Tao Mi^{1

2

3

4}, Liming Jin^{1

2

3

4}, Xin Wu^{1

2

3

4}, Junyi Luo^{1

2

3

4}, Yimeng Liu^{1

2

3

4}, Junhong Liu^{1

2

3

4}, Wenquan Cai^{1

2

3

4

5}, Peng Guo^{1

2

3

4

6}, Dawei He^{1

2

3

4}

Affiliations

¹ Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
² Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China.
³ China International Science and Technology Cooperation Base of Child Development and Critical, National Clinical Research Center for Child Health and Disorders, Chongqing, China.
⁴ Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
⁵ Department of Orthopaedics, Children's Hospital of Chongqing Medical University, Chongqing, China.
⁶ Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.

Abstract

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', 7' -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.