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

Lookup NU author(s): Dr Matthew Barter, Dr Rodolfo Gomez, Kat Cheung, Andrew Skelton, Dr Yaobo Xu, Professor David Young

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Long non-coding RNAs (lncRNAs) are expressed in a highly tissue-specific manner and 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 that plays an essential role in chondrocyte development by directing the expression of chondrocyte-specific genes. Two of these lncRNAs are upregulated during chondrogenic differentiation of mesenchymal stem cells (MSCs). Depletion of one of these lncRNAs, LOC102723505, which we termed ROCR (regulator of chondrogenesis RNA), by RNA interference 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.


Publication metadata

Author(s): Barter MJ, Gomez R, Hyatt S, Cheung K, Skelton AJ, Xu Y, Clark IM, Young DA

Publication type: Article

Publication status: Published

Journal: Development

Year: 2017

Volume: 144

Pages: 4510-4521

Print publication date: 15/12/2017

Online publication date: 18/12/2017

Acceptance date: 25/10/2017

Date deposited: 20/12/2017

ISSN (print): 0950-1991

ISSN (electronic): 1477-9129

Publisher: The Company of Biologists

URL: https://doi.org/10.1242/dev.152504

DOI: 10.1242/dev.152504


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