Long non-coding RNA <i>GRASLND</i> enhances chondrogenesis via suppression of the interferon type II signaling pathway.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32202492.
- Also identified by DOI 10.7554/eLife.49558 and PMC identifier 7202894.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The roles of long noncoding RNAs (lncRNAs) in musculoskeletal development, disease, and regeneration remain poorly understood. Here, we identified the novel lncRNA <i>GRASLND</i> (originally named <i>RNF144A-AS1</i>) as a regulator of mesenchymal stem cell (MSC) chondrogenesis. <i>GRASLND</i>, a primate-specific lncRNA, is upregulated during MSC chondrogenesis and appears to act directly downstream of SOX9, but not TGF-β3. We showed that the silencing of <i>GRASLND</i> resulted in lower accumulation of cartilage-like extracellular matrix in a pellet assay, while <i>GRASLND</i> overexpression - either via transgene ectopic expression or by endogenous activation via CRISPR-dCas9-VP64 - significantly enhanced cartilage matrix production. <i>GRASLND</i> acts to inhibit IFN-γ by binding to EIF2AK2, and we further demonstrated that <i>GRASLND</i> exhibits a protective effect in engineered cartilage against interferon type II. Our results indicate an important role of <i>GRASLND</i> in regulating stem cell chondrogenesis, as well as its therapeutic potential in the treatment of cartilage-related diseases, such as osteoarthritis.
Medical subject headings
- Chondrogenesis
- Gene Expression Regulation, Developmental
- Interferon-gamma
- RNA, Long Noncoding
- Signal Transduction