Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis

• Published in: Cell death discovery 2021-02, Vol.7 (1), p.37-37, Article 37
• Main Authors: Zhou, Yan, Ming, Jianghua, Li, Yaming, Li, Bochun, Deng, Ming, Ma, Yonggang, Chen, Zhonghui, Zhang, Yubiao, Li, Jia, Liu, Shiqing
• Format: Article
• Language: English
• Subjects: 631/80/82/23; 692/308/153; Aging; Apoptosis; Arthritis; Biochemistry; Biomedical and Life Sciences; Cartilage; Cartilage (articular); Cartilage diseases; Cell Biology; Cell Cycle Analysis; Cell death; Cell signaling; Chondrocytes; Degeneration; Exosomes; Fibroblasts; IL-1β; Inflammation; Interleukin 6; Life Sciences; MicroRNAs; miRNA; Osteoarthritis; Osteophytes; Stem Cells; Synovial fluid; Tumor necrosis factor-α
• ISSN: 2058-7716; 2058-7716
• DOI: 10.1038/s41420-021-00418-y

MicroRNAs (miRNAs) encapsulated within exosomes can serve as essential regulators of intercellular communication and represent promising biomarkers of several aging-associated disorders. However, the relationship between exosomal miRNAs and osteoarthritis (OA)-related chondrocytes and synovial fibroblasts (SFCs) remain to be clarified. Herein, we profiled synovial fluid-derived exosomal miRNAs and explored the effects of exosomal miRNAs derived from SFCs on chondrocyte inflammation, proliferation, and survival, and further assessed their impact on cartilage degeneration in a surgically-induced rat OA model. We identified 19 miRNAs within synovial fluid-derived exosomes that were differentially expressed when comparing OA and control patients. We then employed a microarray-based approach to confirm that exosomal miRNA-126-3p expression was significantly reduced in OA patient-derived synovial fluid exosomes. At a functional level, miRNA-126-3p mimic treatment was sufficient to promote rat chondrocyte migration and proliferation while also suppressing apoptosis and IL-1β, IL-6, and TNF-α expression. SFC-miRNA-126-3p-Exos were able to suppress apoptotic cell death and associated inflammation in chondrocytes. Our in vivo results revealed that rat SFC-derived exosomal miRNA-126-3p was sufficient to suppress the formation of osteophytes, prevent cartilage degeneration, and exert anti-apoptotic and anti-inflammatory effects on articular cartilage. Overall, our findings indicate that SFC exosome‐delivered miRNA-126-3p can constrain chondrocyte inflammation and cartilage degeneration. As such, SFC-miRNA-126-3p-Exos may be of therapeutic value for the treatment of patients suffering from OA.