Back to Search
Start Over
Preliminary study on the mechanism by which exosomes derived from human exfoliated deciduous teeth improve the proliferation and osteogenic inhibitory effect of glucocorticoid-induced BMSCs.
- Source :
-
Gene [Gene] 2024 Sep 25; Vol. 923, pp. 148575. Date of Electronic Publication: 2024 May 17. - Publication Year :
- 2024
-
Abstract
- Background: Steroid-induced osteonecrosis of the femoral head (SONFH) is a disease characterized by a collapsed femoral head caused by the overuse of glucocorticoids. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) is an important pathological feature of SONFH. In this study, we investigated whether exosomes from SHEDs (stem cells from human exfoliated deciduous teeth) have a therapeutic effect on glucocorticoid-induced inhibition of proliferation and osteogenesis in BMSCs, and elucidated the underlying mechanisms involved.<br />Methods: Primary dental pulp cells were isolated and cultured from human deciduous tooth pulp, SHEDs were isolated and purified by the limiting dilution method and exosomes were isolated from the supernatants of SHEDs by ultracentrifugation. The cell surface markers CD31, CD34, CD45, CD73, CD90 and CD105 were detected by flow cytometry. A Cell-Counting-Kit-8 assay was used to detect cell activity. ALP and Alizarin Red staining were used to identify osteogenic differentiation ability, and exosomes were identified using transmission electron microscopy, NanoFCM and Western blotting. PKH67 fluorescence was used to track the uptake of exosomes by BMSCs. Transcriptome analysis combined with quantitative real-time PCR was used to explore the underlying mechanism involved.<br />Results: Exosomes secreted by SHEDs can be endocytosed by BMSCs, and can partially reverse the inhibitory effects of glucocorticoids on the viability and osteogenic differentiation of BMSCs. Transcriptome sequencing analysis revealed that the differentially expressed mRNAs regulated by SHED-derived exosomes were enriched mainly in signaling pathways such as the apoptosis pathway, the PI3K-Akt signaling pathway, the Hippo signaling pathway and the p53 signaling pathway. qPCR showed that SHED-derived exosomes reversed the dexamethasone-induced upregulation of HGF and ITGB8 expression and the inhibition of EFNA1 expression, but further increased the dexamethasone-induced downregulation of IL7 expression. In conclusion, SHED-derived exosomes partially reversed the inhibitory effects of glucocorticoids on BMSC proliferation and osteogenesis by inhibiting the expression of HGF, ITGB8 and IL7, and upregulating the expression of EFNA1.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Cells, Cultured
Cell Differentiation drug effects
Dental Pulp cytology
Dental Pulp metabolism
Signal Transduction drug effects
Exosomes metabolism
Exosomes drug effects
Mesenchymal Stem Cells metabolism
Mesenchymal Stem Cells drug effects
Osteogenesis drug effects
Tooth, Deciduous cytology
Tooth, Deciduous metabolism
Cell Proliferation drug effects
Glucocorticoids pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0038
- Volume :
- 923
- Database :
- MEDLINE
- Journal :
- Gene
- Publication Type :
- Academic Journal
- Accession number :
- 38762017
- Full Text :
- https://doi.org/10.1016/j.gene.2024.148575