دورية أكاديمية
Circular RNA from phosphodiesterase 4D can attenuate chondrocyte apoptosis and matrix degradation under OA milieu induced by IL-1β via circPDE4D/miR-4306/SOX9 Cascade.
العنوان: | Circular RNA from phosphodiesterase 4D can attenuate chondrocyte apoptosis and matrix degradation under OA milieu induced by IL-1β via circPDE4D/miR-4306/SOX9 Cascade. |
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المؤلفون: | Gao L; Department of Rehabilitation Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, China., Wang X; Department of Rehabilitation Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, China., Xiong J; Department of Rehabilitation Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, China., Ma Y; Department of Rehabilitation Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan, China. |
المصدر: | Immunopharmacology and immunotoxicology [Immunopharmacol Immunotoxicol] 2022 Oct; Vol. 44 (5), pp. 682-692. Date of Electronic Publication: 2022 May 23. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Informa Healthcare Country of Publication: England NLM ID: 8800150 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-2513 (Electronic) Linking ISSN: 08923973 NLM ISO Abbreviation: Immunopharmacol Immunotoxicol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: London : Informa Healthcare Original Publication: New York, N.Y. : Marcel Dekker, c1987- |
مواضيع طبية MeSH: | MicroRNAs*/genetics , MicroRNAs*/metabolism , Osteoarthritis*/genetics , Osteoarthritis*/metabolism, Annexin A5/metabolism ; Apoptosis ; Biotin/metabolism ; Caspase 3/metabolism ; Chondrocytes/metabolism ; Collagen Type II/metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 4/genetics ; Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism ; Extracellular Matrix/metabolism ; Fluoresceins/metabolism ; Humans ; Interleukin-1beta/metabolism ; Interleukin-6/metabolism ; Interleukin-8 ; Isothiocyanates ; Matrix Metalloproteinase 13/metabolism ; Poly (ADP-Ribose) Polymerase-1/metabolism ; RNA, Circular/genetics ; SOX9 Transcription Factor ; Thrombospondins/metabolism ; bcl-2-Associated X Protein/metabolism |
مستخلص: | Background: Phosphodiesterase 4D (PDE4D) is a novel molecular therapeutic agent for human diseases, including Alzheimer's disease, ischemic stroke, asthma, and cancers. Circular RNA from PDE4D (circPDE4D; ID hsa_circ_0072568) was one of the most downregulated circRNAs in OA patients. However, its precise role in OA-related chondrocytes was largely unknown. Methods: Expressions of circPDE4D, microRNA (miR)-4306, and sex-determining region Y-box 9 (SOX9) were measured by quantitative real-time PCR; protein levels of SOX9 and proteins related to apoptosis and extracellular matrix (ECM) were detected by Western blotting. Cell apoptosis was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, 5-ethynyl-2'-deoxyuridine and Annexin V-fluorescein isothiocyanate apoptosis assays. MiR-4306 response elements were predicted by bioinformatics algorithm and identified using dual-luciferase reporter, RNA immunoprecipitation, and biotin-coupled miRNA capture assays. Results: CircPDE4D was markedly downregulated in OA cartilages and interleukin (IL)-1β-stressed human normal chondrocytes (HNC). Ectopic expression of circPDE4D rescued cell viability, proliferation, and expressions of B-cell lymphoma/leukemia-2 (Bcl-2) and Collagen type II α1 in IL-1β-insulted HNC, and meanwhile declined apoptosis rate and levels of Bcl-2-associated X protein, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase-1, matrix metalloproteinase-13, ADAM metallopeptidase with thrombospondin type 1 motif 5, IL-6, and IL-8. CircPDE4D and SOX9 were competing endogenous RNAs (ceRNAs) for miR-4306, and circPDE4D could positively regulate SOX9 expression via miR-4306. Conclusion: CircPDE4D and miR-4306 were important regulators in regulating IL-1β-induced HNC apoptosis and matrix degradation via regulating the key transcription factor SOX9, suggesting a novel circPDE4D/miR-4306/SOX9 ceRNA pathway in OA-related chondrocyte dysfunction. |
فهرسة مساهمة: | Keywords: CircPDE4D; IL-1β; SOX9; miR-4306; osteoarthritis |
المشرفين على المادة: | 0 (Annexin A5) 0 (Collagen Type II) 0 (Fluoresceins) 0 (Interleukin-1beta) 0 (Interleukin-6) 0 (Interleukin-8) 0 (Isothiocyanates) 0 (MIRN4306 microRNA, human) 0 (MicroRNAs) 0 (RNA, Circular) 0 (SOX9 Transcription Factor) 0 (SOX9 protein, human) 0 (Thrombospondins) 0 (bcl-2-Associated X Protein) 6SO6U10H04 (Biotin) EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1) EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4) EC 3.1.4.17 (PDE4D protein, human) EC 3.4.22.- (Caspase 3) EC 3.4.24.- (Matrix Metalloproteinase 13) |
تواريخ الأحداث: | Date Created: 20220513 Date Completed: 20221004 Latest Revision: 20221011 |
رمز التحديث: | 20240628 |
DOI: | 10.1080/08923973.2022.2077215 |
PMID: | 35549803 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1532-2513 |
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DOI: | 10.1080/08923973.2022.2077215 |