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Objective <p>To investigate the mechanisms by which the RNA-binding protein HuR /ELAVL1 interacts with UFM1 <i>mRNA</i> to ameliorate chondrocyte inflammation, apoptosis, and extracellular matrix (ECM) degradation in osteoarthritis (OA).</p> Methods <p>OA cartilage tissues were collected. A lipopolysaccharide-induced chondrocyte inflammation model was constructed and transfected with relevant sequences or plasmids, chondrocyte viability was detected by MTT, and chondrocyte apoptosis was detected by flow cytometry. OA was induced in rats via anterior cruciate ligament transection (ACLT), and lentiviral vectors mediating overexpression or silencing of HuR/UFM1 were administered via intra-articular injection following surgery. The pathology of cartilage tissue in rats was observed by hematoxylin and eosin staining and safranin O/fast green staining, apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and Collagen II, Aggrecan, MMP3, and MMP13 were measured by immunohistochemistry. Western blot was conducted to measure PCNA, Cleaved-caspase 3, Collagen II, Aggrecan, MMP3 and MMP13. Inflammatory factors in chondrocyte supernatant and rat serum were detected using an enzyme-linked immunosorbent assay. HuR and UFM1 detection was performed using real-time fluorescence quantitative PCR and Western blot. Bioinformatics software, RIP, RNA pull down and mRNA stability analysis were combined to study the binding relationship between HuR and UFM1.</p> Results <p>HuR expression was down-regulated in OA. HuR overexpression ameliorated OA chondrocyte inflammation, apoptosis, and ECM degradation, and HuR downregulation aggravated these pathologies. HuR regulated UFM1 stability by binding to UFM1 3’UTR. UFM1 expression was downregulated in OA and positively correlated with HuR expression. UFM1 silencing counteracted the ameliorative effect of HuR on OA chondrocyte inflammation, apoptosis, and ECM degradation.</p> Conclusion <p>HuR ameliorates OA chondrocyte inflammation, apoptosis, and ECM degradation through post-transcriptional regulation of UFM1.</p>

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RNA-binding protein HuR interacts with UFM1 mRNA to ameliorate chondrocyte inflammation, apoptosis and extracellular matrix degradation

  • 期刊论文

  • 发表日期：

    2025年4月28日

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  • LeXiang Li,
  • Rong Zhou,
  • ZhiPeng Yue,
  • HaoBo Li,
  • YaGuang Han,
  • Lei Zhang,
  • Jun Zhu

摘要

Objective

To investigate the mechanisms by which the RNA-binding protein HuR /ELAVL1 interacts with UFM1 mRNA to ameliorate chondrocyte inflammation, apoptosis, and extracellular matrix (ECM) degradation in osteoarthritis (OA).

Methods

OA cartilage tissues were collected. A lipopolysaccharide-induced chondrocyte inflammation model was constructed and transfected with relevant sequences or plasmids, chondrocyte viability was detected by MTT, and chondrocyte apoptosis was detected by flow cytometry. OA was induced in rats via anterior cruciate ligament transection (ACLT), and lentiviral vectors mediating overexpression or silencing of HuR/UFM1 were administered via intra-articular injection following surgery. The pathology of cartilage tissue in rats was observed by hematoxylin and eosin staining and safranin O/fast green staining, apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and Collagen II, Aggrecan, MMP3, and MMP13 were measured by immunohistochemistry. Western blot was conducted to measure PCNA, Cleaved-caspase 3, Collagen II, Aggrecan, MMP3 and MMP13. Inflammatory factors in chondrocyte supernatant and rat serum were detected using an enzyme-linked immunosorbent assay. HuR and UFM1 detection was performed using real-time fluorescence quantitative PCR and Western blot. Bioinformatics software, RIP, RNA pull down and mRNA stability analysis were combined to study the binding relationship between HuR and UFM1.

Results

HuR expression was down-regulated in OA. HuR overexpression ameliorated OA chondrocyte inflammation, apoptosis, and ECM degradation, and HuR downregulation aggravated these pathologies. HuR regulated UFM1 stability by binding to UFM1 3’UTR. UFM1 expression was downregulated in OA and positively correlated with HuR expression. UFM1 silencing counteracted the ameliorative effect of HuR on OA chondrocyte inflammation, apoptosis, and ECM degradation.

Conclusion

HuR ameliorates OA chondrocyte inflammation, apoptosis, and ECM degradation through post-transcriptional regulation of UFM1.