Author:
Jin Zhuangzhuang,Zhang He,Bai Lunhao,Yue Lingyu,Zhang Weiming,Liang Jiajian,Chang Bohan,Yang Yue,Hu Zhehan,Chen Liang,Guo Chuanji
Abstract
Abstract
Background
The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients.
Methods
The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and Fe2+ in both serum and synovium.
Results
JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and Fe2+ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level.
Conclusions
The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis.
Funder
National Natural Science Foundation of China
the Fundamental Research Project of Liaoning Provincial Department of Education
the General Project of Shengjing Hospital in 2022
the 345 Talent Project of Shengjing Hospital
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Cited by
2 articles.
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