IL-4 promotes chondrogenesis of bone marrow mesenchymal stem cells and blockade of IL-4Rα retards the endochondral ossification during rat embryonic bone development.
BMSCs
IL‐4/IL‐4Rα
chondrogenesis
embryonic bone development
Journal
Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422
Informations de publication
Date de publication:
13 Oct 2024
13 Oct 2024
Historique:
revised:
19
08
2024
received:
19
04
2024
accepted:
12
09
2024
medline:
14
10
2024
pubmed:
14
10
2024
entrez:
13
10
2024
Statut:
aheadofprint
Résumé
Interleukin-4 (IL-4)/IL-4 receptor alpha (IL-4Rα) signalling pathways play important roles in the complex process of bone formation and bone remodelling. However, whether IL-4/IL-4Rα participates in skeletogenesis during embryonic development is not completely understood. We used the anti-IL-4Rα monoclonal antibody (anti-IL-4Rα mAb) as a powerful investigational tool to evaluate the potential roles of IL-4/IL-4Rα in the chondrogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. Simultaneously, we explored the effect of IL-4/IL-4Rα on bone ossification during rat embryo-fetal development. In this study, we found that, compared to the control group, IL-4 can significantly promote the chondrogenic differentiation of BMSCs. Furthermore, following exposure to anti-IL-4Rα mAb in pregnant rats, unexpected phenomena were observed in fetal bone development, including non-ossification of the fetal sternum, an incomplete ossification centre in long bones and a reduced number of ossification points in digit (toe) bones. To further investigate the underlying mechanism of the phenotype, we studied the rat sternum as the target organ, starting from different time points of sternum development in the embryonic stage. The results indicated that the retardation mainly occurred in the middle and late stages of embryonic development. This retardation was characterized by the inhibition of the differentiation process of mesenchymal stem cells into chondrocytes, resulting in reduced angiogenesis near the ossification centre, failure of osteoblasts to invade the centre of the cartilage body with the blood vessels and delayed formation of the primary ossification centre (POC). Overall, our study demonstrated the significant function of IL-4/IL-4Rα in chondrogenic differentiation of BMSCs and bone ossification during embryo-fetal development.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Shanghai Clinical Research Plan of SHCD
Organisme : Shanghai Municipal Health and Family Planning Commission
ID : 202040352
Organisme : Shanghai Rising-Star Program
ID : 20QA1408700
Informations de copyright
© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.
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