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RNA binding proteins regulate anabolic and catabolic gene expression in chondrocytes

B T McDermott1, S Ellis1, G Bou-Gharios1

  • 1Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Leahurst Campus, Neston, Cheshire CH64 7TE, UK.

Osteoarthritis and Cartilage
|February 9, 2016
PubMed
Abstract

Insights

RNA binding proteins (RNABPs) regulate cartilage homeostasis by controlling anabolic and catabolic gene expression. Tristetraprolin (TTP) knockdown increases SOX9 and aggrecan, while HuR knockdown increases MMP13, revealing novel post-transcriptional control mechanisms.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Articular cartilage homeostasis relies on balancing anabolic and catabolic factors.
  • RNA binding proteins (RNABPs) are implicated in regulating gene expression.

Purpose of the Study:

  • To investigate the role of RNABPs in regulating anabolic (SOX9, Aggrecan) and catabolic (MMP13) gene expression in chondrocytes.
  • To elucidate the post-transcriptional mechanisms by which RNABPs influence cartilage homeostasis.

Main Methods:

  • Small interfering RNA (siRNA) was used to knock down RNABP expression in SW1353 chondrosarcoma cells and human articular chondrocytes (HACs).
  • Gene expression and mRNA decay were analyzed using reverse transcription quantitative polymerase chain reaction (RT-qPCR).
  • RNA-electromobility shift assays (EMSAs) and immunohistochemistry were employed to study RNABP interactions and localization.

Main Results:

  • Knockdown of tristetraprolin (TTP) increased SOX9 mRNA, mRNA half-life, and protein expression, as well as aggrecan mRNA expression in both cell types.
  • RNA-EMSAs confirmed TTP interaction with AU-rich elements in the SOX9 mRNA 3' untranslated region (UTR).
  • Knockdown of human antigen R (HuR) significantly increased matrix metalloproteinase (MMP)13 expression and affected known transcriptional repressors of MMP13.

Conclusions:

  • RNABPs play a critical role in modulating the balance of anabolic and catabolic gene expression in human chondrocytes.
  • Post-transcriptional regulation by RNABPs offers novel mechanisms for controlling SOX9 and MMP13 expression.
  • These findings suggest potential therapeutic targets for cartilage-related disorders.
Keywords:
ChondrocyteMMP13SOX9mRNA

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