Inflammatory priming of human mesenchymal stem cells induces osteogenic differentiation via the early response gene IER3.
BST2
ERK1/2
IER3
bone formation
inflammation
mesenchymal stem cells
osteoblasts
osteogenic differentiation
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
15 Oct 2024
15 Oct 2024
Historique:
revised:
27
08
2024
received:
14
06
2024
accepted:
16
09
2024
medline:
7
10
2024
pubmed:
7
10
2024
entrez:
7
10
2024
Statut:
ppublish
Résumé
Mesenchymal stem cells (MSCs) have gained tremendous interest due to their overall potent pro-regenerative and immunomodulatory properties. In recent years, various in vitro and preclinical studies have investigated different priming ("licensing") approaches to enhance MSC functions for specific therapeutic purposes. In this study, we primed bone marrow-derived human MSCs (hMSCs) with an inflammation cocktail designed to mimic the elevated levels of inflammatory mediators found in serum of patients with severe injuries, such as bone fractures. We observed a significantly enhanced osteogenic differentiation potential of primed hMSCs compared to untreated controls. By RNA-sequencing analysis, we identified the immediate early response 3 (IER3) gene as one of the top-regulated genes upon inflammatory priming. Small interfering RNA knockdown experiments established IER3 as a novel positive regulator of osteogenic differentiation. Mechanistic analysis further revealed that IER3 deletion significantly downregulated bone marrow stromal cell antigen 2 (BST2) expression and extracellular signal-related kinase 1/2 (ERK1/2) phosphorylation in hMSCs, suggesting that IER3 regulates osteogenic differentiation through BST2 and ERK1/2 signaling pathway activation. On the basis of these findings, we propose IER3 as a novel therapeutic target to promote hMSC osteoblastogenesis, which might be of high clinical relevance, for example, in patients with osteoporosis or compromised fracture healing.
Identifiants
pubmed: 39373973
doi: 10.1096/fj.202401344R
doi:
Substances chimiques
Antigens, CD
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e70076Subventions
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 251293561
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : B09 INST 40/682-1
Organisme : Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg (MWK)
ID : MWK25-0123-139/1/11
Informations de copyright
© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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