Sub-toxic levels of cobalt ions impair chondrocyte mechanostranduction via HDAC6-dependent primary cilia shortening.

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  • Author(s): Wu H;Wu H; Wang Z; Wang Z; Liu S; Liu S; Meng H; Meng H; Liu S; Liu S; Fu S; Fu S
  • Source:
    Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2021 Mar 12; Vol. 544, pp. 38-43. Date of Electronic Publication: 2021 Jan 28.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Mechanotransduction, Cellular*; Anilides/*pharmacology ; Chondrocytes/*pathology ; Cilia/*pathology ; Cobalt/*toxicity ; Hydroxamic Acids/*pharmacology ; Matrix Metalloproteinase 13/*metabolism; Animals ; Cattle ; Cells, Cultured ; Chondrocytes/drug effects ; Chondrocytes/metabolism ; Cilia/drug effects ; Cilia/metabolism ; Histone Deacetylase Inhibitors/pharmacology ; Trace Elements/toxicity
    • Abstract:
      Cobalt ions are the main wear particles associated with orthopaedic implants, causing adverse complications due to cytotoxicity and inflammatory mediators. Recent studies have shown that sub-toxic levels of cobalt ions regulate matrix synthesis and inflammation, but the influence of cobalt ions on mechanotransduction remains unclear. Previously, we reported that sub-toxic levels of cobalt ions modulated primary cilia, which are crucial for mechanotransduction. This study therefore aimed to investigate the effect of cobalt ions on chondrocyte mechanosensation in response to cyclic tensile strain and the association with primary cilia. Sub-toxic levels of cobalt ions impaired chondrocyte mechanosensation and affected the gene expression of aggrecan, collagen II and MMP-13. Moreover, cobalt ions induced HDAC6-dependent primary cilia disassembly, which was associated with either cytoplasmic or ciliary α-tubulin deacetylation. Pharmaceutical HDAC6 inhibition with tubacin restored primary cilia length and mechanotransduction, whereas chemical depletion of primary cilia by chloral hydrate prevented mechanosignalling. Thus, sub-toxic levels of cobalt ions impaired chondrocyte mechanotransduction via HDAC6 activation, which was associated with tubulin deacetylation and primary cilia shortening.
      (Copyright © 2021 Elsevier Inc. All rights reserved.)
    • Comments:
      Erratum in: Biochem Biophys Res Commun. 2021 May 28;555:213. (PMID: 33867123)
    • Grant Information:
      MR/L002876/1 United Kingdom MRC_ Medical Research Council
    • Contributed Indexing:
      Keywords: Chondrocytes; Cobalt; Mechanotransduction; Primary cilia
    • Accession Number:
      0 (Anilides)
      0 (Histone Deacetylase Inhibitors)
      0 (Hydroxamic Acids)
      0 (Trace Elements)
      02C2G1D30D (tubacin)
      3G0H8C9362 (Cobalt)
      EC 3.4.24.- (Matrix Metalloproteinase 13)
    • Publication Date:
      Date Created: 20210131 Date Completed: 20210831 Latest Revision: 20210831
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.bbrc.2021.01.041
    • Accession Number:
      33516880