Long non-coding RNA GRASLND enhances chondrogenesis via suppression of interferon type II signaling pathway
- Washington University in St Louis, United States
- Vanderbilt University, United States
Abstract
The roles of long noncoding RNAs (lncRNAs) in musculoskeletal development, disease, and regeneration remain poorly understood. Here, we identified the novel lncRNA GRASLND (originally named RNF144A-AS1) as a regulator of mesenchymal stem cell (MSC) chondrogenesis. GRASLND, a primate-specific lncRNA, is upregulated during MSC chondrogenesis and appears to act directly downstream of SOX9, but not TGF-b3. We showed that the silencing of GRASLND resulted in lower accumulation of cartilage-like extracellular matrix in a pellet assay, while GRASLND overexpression – either via transgene ectopic expression or by endogenous activation via CRISPR-dCas9-VP64 – significantly enhanced cartilage matrix production. GRASLND acts to inhibit IFN-γ by binding to EIF2AK2, and we further demonstrated that GRASLND exhibits a protective effect in engineered cartilage against interferon type II. Our results indicate an important role of GRASLND in regulating stem cell chondrogenesis, as well as its therapeutic potential in the treatment of cartilage-related diseases, such as osteoarthritis.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE129985.
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Long non-coding RNA GRASLND enhances chondrogenesis via suppression of interferon type II signaling pathwayNCBI Gene Expression Omnibus, GSE129985.
Article and author information
Author details
Funding
Arthritis Foundation
- Farshid Guilak
Nancy Taylor Foundation for Chronic Diseases
- Farshid Guilak
National Institutes of Health
- Farshid Guilak
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Clifford J Rosen, Maine Medical Center Research Institute, United States
Publication history
- Received: June 21, 2019
- Accepted: March 21, 2020
- Accepted Manuscript published: March 23, 2020 (version 1)
- Version of Record published: May 6, 2020 (version 2)
Copyright
© 2020, Huynh et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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