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


Huynh NPNguyen Pt , Gloss CCCatherine C , Lorentz JJeremiah , Tang RRuhang , Brunger JMJonathan M , McAlinden AAudrey , Zhang BBo , Guilak FFarshid . eLife. 2020 3 23; 9().


The roles of long noncoding RNAs (lncRNAs) in musculoskeletal development, disease, and regeneration remain poorly understood. Here, we identified the novel lncRNA (originally named ) as a regulator of mesenchymal stem cell (MSC) chondrogenesis. , 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 resulted in lower accumulation of cartilage-like extracellular matrix in a pellet assay, while overexpression – either via transgene ectopic expression or by endogenous activation via CRISPR-dCas9-VP64 – significantly enhanced cartilage matrix production. acts to inhibit IFN-γ by binding to EIF2AK2, and we further demonstrated that exhibits a protective effect in engineered cartilage against interferon type II. Our results indicate an important role of in regulating stem cell chondrogenesis, as well as its therapeutic potential in the treatment of cartilage-related diseases, such as osteoarthritis.