Long non-coding RNA ROCR contributes to SOX9 expression and chondrogenic differentiation of human mesenchymal stem cells

Matthew Barter, Rodolfo Gomez, Sam Hyatt, Kat Cheung, Andrew Skelton, Yaobo Xu, Ian Clark, David Young

Research output: Contribution to journalArticle

43 Citations (Scopus)
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Abstract

Long non-coding RNAs (lncRNAs) are expressed in a highly tissue-specific manner where they function in various aspects of cell biology, often as key regulators of gene expression. In this study we established a role for lncRNAs in chondrocyte differentiation. Using RNA sequencing we identified a human articular chondrocyte repertoire of lncRNAs from normal hip cartilage donated by neck of femur fracture patients. Of particular interest are lncRNAs upstream of the master chondrocyte transcription factor SOX9 locus. SOX9 is an HMG-box transcription factor which is essential for chondrocyte development by directing the expression of chondrocyte specific genes. Two of these lncRNAs are upregulated during chondrogenic differentiation of MSCs. Depletion of one of these lncRNA, LOC102723505, which we termed ROCR (regulator of chondrogenesis RNA), by RNAi disrupted MSC chondrogenesis, concomitant with reduced cartilage-specific gene expression and incomplete matrix component production, indicating an important role in chondrocyte biology. Specifically, SOX9 induction was significantly ablated in the absence of ROCR, and overexpression of SOX9 rescued the differentiation of MSCs into chondrocytes. Our work sheds further light on chondrocyte specific SOX9 expression and highlights a novel method of chondrocyte gene regulation involving a lncRNA.
Original languageEnglish
Pages (from-to)4510-4521
JournalDevelopment
Volume144
Issue number24
Early online date30 Oct 2017
DOIs
Publication statusPublished - 15 Dec 2017

Keywords

  • SOX9
  • LncRNA
  • Cartilage
  • Chondrogenesis
  • MSC
  • Epigenetics
  • Differentiation

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