Unraveling the Exosome-Derived ceRNA Network of Cartilage Injury in Kashin-Beck Disease Chondrocytes.

Authors

Chaowei Wang, Lulu Bai, Liangyu Cui, Pengyan Jiao, Zhouyun Chen, Yang Liu, Yirong Qin, Hui Wang, Lian Liu, Qi Jing, Yuyang Ma, Yuequan Yuan, Xi Lv, Yu Zhang, Feihong Chen, Yujie Ning, Shujin Li, Xi Wang

Published in

Biological trace element research. Jul 06, 2026. Epub Jul 06, 2026.

Abstract

This study sought to develop and validate an exosome-derived competitive endogenous RNA (ceRNA) regulatory network in chondrocytes impacted by Kashin-Beck disease (KBD) and to elucidate its functional implications in selenium deficiency-induced cartilage damage. Exosomes were isolated from the chondrocytes of KBD patients (n = 3) and matched healthy controls (n = 3). Exosomal RNA microarrays and high-throughput miRNA sequencing were employed to identify differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) using predefined thresholds of |fold change| ≧ 1, P < 0.05, or TargetScan_score ≧ 50 and miranda_Energy < - 10. Through an integration of bioinformatics analysis and experimental approaches, we constructed a KBD-specific exosome-derived ceRNA network and validated the expression patterns of core molecules in C28/I2 chondrocyte and SD rat models. Transcriptomic profiling revealed numerous dysregulated exosomal lncRNAs, miRNAs, and mRNAs in KBD chondrocytes, which were predominantly enriched in pathways associated with cartilage damage, oxidative stress, and extracellular matrix metabolism. Furthermore, a comprehensive analysis identified six distinct lncRNA-miRNA-mRNA regulatory axes within the ceRNA network, encompassing five lncRNAs, miR-423-5p, miR-654-5p, and their target genes CDC42 and SETD8. Validation through RT-qPCR and immunohistochemistry (IHC) revealed aberrant expression patterns in KBD induced by selenium deficiency: lncRNAs were markedly upregulated, miRNAs were significantly downregulated, and both CDC42 and SETD8 were substantially upregulated. These findings imply that exosome-derived ceRNA interactions may play a role in selenium deficiency-associated cartilage damage by modulating CDC42 and SETD8. In conclusion, this exploratory study systematically constructs and preliminarily validates an exosome-derived ceRNA network in KBD chondrocytes. The results indicate that this network may mediate cartilage damage induced by selenium deficiency and T-2 toxin via the lncRNA-miR-423-5p/miR-654-5p-CDC42/SETD8 axes. These molecules hold potential as candidate diagnostic biomarkers for KBD, although further validation in larger cohorts is necessary.

PMID:
42406332
Bibliographic data and abstract were imported from PubMed on 06 Jul 2026.

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