CDK5 Upregulated by ELF3 Transcription Promotes IL-1β-induced Inflammation and Extracellular Matrix Degradation in Human Chondrocytes.

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      Publisher: Humana Press Country of Publication: United States NLM ID: 9701934 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0283 (Electronic) Linking ISSN: 10859195 NLM ISO Abbreviation: Cell Biochem Biophys Subsets: MEDLINE
    • Publication Information:
      Original Publication: Totowa, NJ : Humana Press, c1996-
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    • Abstract:
      Osteoarthritis (OA) is a common chronic disease with age-associated increase in both incidence and prevalence. The cyclin-dependent kinase 5 (CDK5), which is a member of the CDK family, is involved in many chronic diseases. This study was performed to explore the functional role of CDK5 in OA and to discuss the detailed molecular mechanisms. The expressions of CDK5 and ELF3 before or after transfection were detected with reverse transcription-quantitative PCR (RT-qPCR) and western blot. 5-ethynyl-2'-deoxyuridine (Edu) and terminal deoxynucleoitidyl transferase-mediated nick-end labeling (TUNEL) assays were used to detect the proliferation and apoptosis of C28/I2 cells. The levels of inflammatory cytokines were estimated using enzyme-linked immunosorbent assay (ELISA) while the expressions of proteins implicated in extracellular matrix (ECM) degradation- and apoptosis were detected using western blot. Additionally, the activity of CDK5 promoters and its binding with ELF3 were detected using luciferase activity assay and chromatin immunoprecipitation (CHIP) assay. In the present study, it was discovered that the mRNA and protein expressions of CDK5 were significantly increased in IL-1β-induced C28/I2 cells. After depleting CDK5 expression, the apoptosis, inflammation and ECM in C28/I2 cells with IL-1β induction were suppressed. It was also found that ELF3 expression was increased in IL-1β-induced C28/I2 cells and acted as a transcription factor binding to the CDK5 promoter to regulate its transcriptional expression. The further experiments evidenced that ELF3 overexpression partially reversed the inhibitory effects of CDK5 deficiency on IL-1β-induced apoptosis, inflammation and ECM in C28/I2 cells. Collectively, CDK5 that upregulated by ELF3 transcription could promote the development of OA.
      Competing Interests: Compliance with Ethical Standards Conflict of interest The authors declare no competing interests.
      (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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    • Grant Information:
      GF20H060018 2020 Basic Public Welfare Research Program of Zhejiang Province
    • Contributed Indexing:
      Keywords: CDK5; ELF3; Extracellular matrix degradation; Inflammation; Osteoarthritis
    • Accession Number:
      0 (Interleukin-1beta)
      0 (Transcription Factors)
      EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
      0 (ELF3 protein, human)
      0 (DNA-Binding Proteins)
      0 (Proto-Oncogene Proteins c-ets)
    • Publication Date:
      Date Created: 20240717 Date Completed: 20241119 Latest Revision: 20241212
    • Publication Date:
      20241212
    • Accession Number:
      10.1007/s12013-024-01415-5
    • Accession Number:
      39020088