دورية أكاديمية
A novel mechanism behind irreversible development of cartilage degradation driven articular cartilage defects revealed by rat model: The chain reaction initiated by extracellular vesicles delivered LOC102546541.
| العنوان: | A novel mechanism behind irreversible development of cartilage degradation driven articular cartilage defects revealed by rat model: The chain reaction initiated by extracellular vesicles delivered LOC102546541. |
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| المؤلفون: | Lai C; Department of Orthopaedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Cheng X; Department of Orthopaedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Yuan T; Department of Orthopaedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Fang P; Department of Orthopaedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Qian H; Department of Orthopaedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Jiang H; Department of Orthopaedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Meng J; Department of Orthopaedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China., Zhao J; Department of Orthopaedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: zhaojianning.0207@163.com., Bao N; Department of Orthopaedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: bnrbnr@sina.com., Zhang L; Department of Orthopaedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address: leizhang1987md@163.com. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112467. Date of Electronic Publication: 2024 Jun 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Extracellular Vesicles*/metabolism , Cartilage, Articular*/metabolism , Cartilage, Articular*/pathology , Chondrocytes*/metabolism , RNA, Long Noncoding*/genetics , RNA, Long Noncoding*/metabolism , Osteoarthritis*/metabolism , Osteoarthritis*/pathology , Matrix Metalloproteinase 13*/metabolism , Matrix Metalloproteinase 13*/genetics , Disease Models, Animal* , MicroRNAs*/genetics , MicroRNAs*/metabolism, Animals ; Rats ; Rats, Sprague-Dawley ; Male ; Humans ; Cells, Cultured ; RNA, Small Interfering/genetics |
| مستخلص: | Background: Articular cartilage defects (ACD) are injuries with a diameter greater than 3 mm, resulting from wear and tear on joints. When the diameter of the defect exceeds 6 mm, it can further damage the surrounding joint cartilage, causing osteoarthritis (OA). Try to explain why OA is an irreversible disease, we hypothesize that damaged articular chondrocytes (DAC) may have reduced capacities to repair cartilage because its extracellular vesicle (EVs) that might directly contribute to OA formation. Methods: In this study, DAC-EVs and AC-EVs were isolated using ultracentrifugation. Next-generation sequencing was employed to screen for a pathogenic long non-coding RNA (lncRNA). After verifying its function in vitro, the corresponding small interfering RNA (siRNA) was constructed and loaded into extracellular vesicles, which were then injected into the knee joint cavities of rats. Results: The results revealed that DAC-EVs packaged lncRNA LOC102546541 acts as a competitive endogenous RNA (ceRNA) of MMP13, down-regulating miR-632. Consequently, the function of MMP13 in degrading the extracellular matrix is enhanced, promoting the development of osteoarthritis. Conclusions: This study uncovered a novel mode of OA pathogenesis using rat models, which DAC deliver pathogenic LOC102546541 packaged EVs to normal articular chondrocytes, amplifying the degradation of the extracellular matrix. Nonetheless, the functions of highly homologous human gene of LOC102546541 need to be verified in the future. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Articular cartilage defects; Damaged articular chondrocytes; Extracellular matrix; Extracellular vesicles; lncRNA |
| المشرفين على المادة: | 0 (RNA, Long Noncoding) EC 3.4.24.- (Matrix Metalloproteinase 13) 0 (MicroRNAs) 0 (RNA, Small Interfering) |
| تواريخ الأحداث: | Date Created: 20240614 Date Completed: 20240710 Latest Revision: 20240710 |
| رمز التحديث: | 20240710 |
| DOI: | 10.1016/j.intimp.2024.112467 |
| PMID: | 38875997 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2024.112467 |