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Long non-coding RNA GRASLND enhances chondrogenesis via suppression of the interferon type II signaling pathway.

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-?3. 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-? 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.

SUBMITTER: Huynh NP 

PROVIDER: S-EPMC7202894 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Long non-coding RNA <i>GRASLND</i> enhances chondrogenesis via suppression of the interferon type II signaling pathway.

Huynh Nguyen Pt NP   Gloss Catherine C CC   Lorentz Jeremiah J   Tang Ruhang R   Brunger Jonathan M JM   McAlinden Audrey A   Zhang Bo B   Guilak Farshid F  

eLife 20200323

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 accumula  ...[more]

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