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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.
Lai, Chengteng; Cheng, Xi; Yuan, Tao; Fang, Peng; Qian, Hong; Jiang, Hui; Meng, Jia; Zhao, Jianning; Bao, Nirong; Zhang, Lei.
Affiliation
  • 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.
Int Immunopharmacol ; 137: 112467, 2024 Aug 20.
Article de En | MEDLINE | ID: mdl-38875997
ABSTRACT

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.
Sujet(s)
Mots clés

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Arthrose / Cartilage articulaire / Chondrocytes / MicroARN / Modèles animaux de maladie humaine / Matrix Metalloproteinase 13 / ARN long non codant / Vésicules extracellulaires Limites: Animals / Humans / Male Langue: En Journal: Int Immunopharmacol / Int. immunopharmacol / International immunopharmacology Sujet du journal: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Année: 2024 Type de document: Article Pays d'affiliation: Chine Pays de publication: Pays-Bas

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Arthrose / Cartilage articulaire / Chondrocytes / MicroARN / Modèles animaux de maladie humaine / Matrix Metalloproteinase 13 / ARN long non codant / Vésicules extracellulaires Limites: Animals / Humans / Male Langue: En Journal: Int Immunopharmacol / Int. immunopharmacol / International immunopharmacology Sujet du journal: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Année: 2024 Type de document: Article Pays d'affiliation: Chine Pays de publication: Pays-Bas