Impaired chondrocyte U3 snoRNA expression in osteoarthritis impacts the chondrocyte protein translation apparatus

E.G.J. Ripmeester, M.M.J. Caron, G.G.H. van den Akker, D.A.M. Surtel, A. Cremers, P. Balaskas, P. Dyer, B.A.C. Housmans, A. Chabronova, A. Smagul, Y.X. Fang, L.W. van Rhijn, M.J. Peffers, T.J.M. Welting*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

Although pathways controlling ribosome activity have been described to regulate chondrocyte homeostasis in osteoarthritis, ribosome biogenesis in osteoarthritis is unexplored. We hypothesized that U3 snoRNA, a non-coding RNA involved in ribosomal RNA maturation, is critical for chondrocyte protein translation capacity in osteoarthritis. U3 snoRNA was one of a number of snoRNAs with decreased expression in osteoarthritic cartilage and osteoarthritic chondrocytes. OA synovial fluid impacted U3 snoRNA expression by affecting U3 snoRNA gene promoter activity, while BMP7 was able to increase its expression. Altering U3 snoRNA expression resulted in changes in chondrocyte phenotype. Interference with U3 snoRNA expression led to reduction of rRNA levels and translational capacity, whilst induced expression of U3 snoRNA was accompanied by increased 18S and 28S rRNA levels and elevated protein translation. Whole proteome analysis revealed a global impact of reduced U3 snoRNA expression on protein translational processes and inflammatory pathways. For the first time we demonstrate implications of a snoRNA in osteoarthritis chondrocyte biology and investigated its role in the chondrocyte differentiation status, rRNA levels and protein translational capacity.
Original languageEnglish
Article number13426
Number of pages14
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 10 Aug 2020

Keywords

  • analysis reveals
  • apoptosis
  • biogenesis
  • endoplasmic-reticulum stress
  • hypertrophy
  • p53
  • pathogenesis
  • pre-ribosomal-rna
  • progression
  • proteomic analysis
  • ANALYSIS REVEALS
  • APOPTOSIS
  • ENDOPLASMIC-RETICULUM STRESS
  • PRE-RIBOSOMAL-RNA
  • P53
  • PATHOGENESIS
  • HYPERTROPHY
  • BIOGENESIS
  • PROTEOMIC ANALYSIS
  • PROGRESSION

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