دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Long non-coding RNA GRASLND enhances chondrogenesis via suppression of the interferon type II signaling pathway.
المؤلفون: Huynh NP; Department of Orthopaedic Surgery, Washington University, St Louis, United States.; Shriners Hospitals for Children, St. Louis, United States.; Department of Cell Biology, Duke University, Durham, United States.; Center of Regenerative Medicine, Washington University, St Louis, United States., Gloss CC; Department of Orthopaedic Surgery, Washington University, St Louis, United States.; Shriners Hospitals for Children, St. Louis, United States.; Center of Regenerative Medicine, Washington University, St Louis, United States., Lorentz J; Department of Orthopaedic Surgery, Washington University, St Louis, United States.; Shriners Hospitals for Children, St. Louis, United States.; Center of Regenerative Medicine, Washington University, St Louis, United States., Tang R; Department of Orthopaedic Surgery, Washington University, St Louis, United States.; Shriners Hospitals for Children, St. Louis, United States.; Center of Regenerative Medicine, Washington University, St Louis, United States., Brunger JM; Department of Biomedical Engineering, Vanderbilt University, Nashville, United States., McAlinden A; Department of Orthopaedic Surgery, Washington University, St Louis, United States.; Shriners Hospitals for Children, St. Louis, United States.; Center of Regenerative Medicine, Washington University, St Louis, United States., Zhang B; Center of Regenerative Medicine, Washington University, St Louis, United States., Guilak F; Department of Orthopaedic Surgery, Washington University, St Louis, United States.; Shriners Hospitals for Children, St. Louis, United States.; Center of Regenerative Medicine, Washington University, St Louis, United States.
المصدر: ELife [Elife] 2020 Mar 23; Vol. 9. Date of Electronic Publication: 2020 Mar 23.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Gene Expression Regulation, Developmental* , Signal Transduction*, Chondrogenesis/*genetics , Interferon-gamma/*metabolism , RNA, Long Noncoding/*genetics, Binding Sites ; Cell Differentiation/genetics ; Cells, Cultured ; Chondrocytes/cytology ; Extracellular Matrix/metabolism ; Gene Editing ; Gene Expression Profiling ; Gene Regulatory Networks ; Humans ; Immunohistochemistry ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Protein Binding
مستخلص: 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-β3. 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.
Competing Interests: NH, CG, JL, RT, JB, AM, BZ, FG No competing interests declared
(© 2020, Huynh et al.)
التعليقات: Comment in: Elife. 2020 May 06;9:. (PMID: 32374717)
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معلومات مُعتمدة: P30 AR073752 United States AR NIAMS NIH HHS; P01 AR050245 United States AR NIAMS NIH HHS; R01 AR069605 United States AR NIAMS NIH HHS; R01 AR075730 United States AR NIAMS NIH HHS; R01 AG046927 United States AG NIA NIH HHS; R01 AR064191 United States AR NIAMS NIH HHS; P30 AR074992 United States AR NIAMS NIH HHS; R21 AR072193 United States AR NIAMS NIH HHS; R01 AG015768 United States AG NIA NIH HHS
فهرسة مساهمة: Keywords: RNF144A-AS1; human; mesenchymal stem cells; regenerative medicine; stem cells; tissue engineering
سلسلة جزيئية: GEO GSE129985; GSE109503; GSE69110; GSE57218
المشرفين على المادة: 0 (RNA, Long Noncoding)
82115-62-6 (Interferon-gamma)
تواريخ الأحداث: Date Created: 20200324 Date Completed: 20210330 Latest Revision: 20221209
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7202894
DOI: 10.7554/eLife.49558
PMID: 32202492
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.49558