Department of Emergence Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Bone and Soft Tissue Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
J Transl Med. 2023 Sep 23;21(1):661. doi: 10.1186/s12967-023-04541-5.
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.
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 Fe in both serum and synovium.
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 Fe were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level.
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.
骨关节炎（OA）的防治是其研究中的一个主要挑战。滑膜是系统性治疗 OA 的关键组织。本研究旨在探讨 OA 患者铁过载相关的潜在靶基因及其相关性。
分析的内部数据集包括微阵列数据集 GSE46750、GSE55457 和 GSE56409，验证的外部数据集包括 GSE12021 和 GSE55235。使用 GSE176308 数据集生成单细胞 RNA 测序图谱。为了研究靶基因在滑膜样本中的表达，进行了定量逆转录-PCR、western blot 和免疫组织化学检测。酶联免疫吸附试验用于检测血清和滑膜中铁蛋白和 Fe 的水平。
从差异表达基因中筛选出 JUN 和 ZFP36，OA 滑膜中的 mRNA 水平明显低于正常滑膜。随后，在 OA 滑膜中观察到复杂且动态演变的细胞成分。OA 滑膜中不同细胞簇的 JUN 和 ZFP36 mRNA 水平不同，与免疫细胞浸润相关。此外，OA 患者的血清和滑膜中铁蛋白和 Fe 水平显著升高。进一步发现 JUN 蛋白水平升高，ZFP36 蛋白水平降低。
滑膜是反映 OA 患者系统性铁过载不良影响的敏感组织。JUN 和 ZFP36 可能是减轻 OA 治疗中铁过载的潜在靶基因。JUN 的转录和蛋白水平之间存在一些差异，提示可能涉及转录后修饰。未来的研究还应关注 JUN 和 ZFP36 在诱导 OA 发病过程中滑膜细胞成分变化中的作用。
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