Key Takeaways & Executive Findings
- •• Synovial fluid exosomes mediate bidirectional signaling between synoviocytes and chondrocytes, playing a dual role in knee osteoarthritis progression by both aggravating and protecting against cartilage degeneration and synovial inflammation. • Dynamic changes in exosomal non-coding RNAs (e.g., miR-140-5p, miR-21-5p, circ_0001236) correlate with disease stage, suggesting exosomes as potential liquid biopsy biomarkers for knee osteoarthritis. • Multi-omics and single-cell sequencing combined with exosome profiling reveal that synovial fluid exosomes regulate not only the classical NF-κB pathway but also emerging pathways such as ferroptosis, pyroptosis, and immunometabolic reprogramming. • Engineered exosomes, particularly mesenchymal stem cell-derived exosomes enriched with specific miRNAs (e.g., miR-140-3p, miR-26a-5p), show promise for enhancing anti-inflammatory effects and targeted therapy in knee osteoarthritis.
Abstract
BACKGROUND: Increasing evidence has demonstrated the crucial role of synovial cell-chondrocyte signaling crosstalk mediated by synovial fluid exosomes in knee osteoarthritis. The signaling interaction between synovial cells and chondrocytes reveals, at the molecular level, the bidirectional regulatory role of synovial fluid exosomes in the progression of knee osteoarthritis. OBJECTIVE: To comprehensively interpret the interactions between synoviocytes and chondrocytes mediated by synovial fluid exosomes from multiple perspectives and levels to provide new insights and directions for research and clinical applications in the related field. METHODS: A literature search was conducted in PubMed for publications from January 2001 to June 2025 using the keywords “osteoarthritis*, exosomes, synovial cells, chondrocytes.” All relevant original studies, reviews, and clinical trials published from January 2001 to June 2025 were included, while irrelevant mechanisms and low-relevance studies were excluded. Finally, 93 articles were selected for comprehensive analysis. RESULTS AND CONCLUSION: During the development and progression of knee osteoarthritis, synovial cells and chondrocytes establish close signal communication via synovial fluid exosomes. This signaling interaction significantly affects the progression of knee osteoarthritis, potentially exacerbating cartilage degeneration and synovial inflammation, while also exerting protective regulatory effects under specific conditions. Therefore, the dual nature of this mechanism highlights the necessity for precise intervention, and targeting key molecules in exosome-mediated intercellular signaling pathways may offer new therapeutic strategies and targets for knee osteoarthritis.
1. Introduction
Knee osteoarthritis is a chronic degenerative joint disease characterized by articular cartilage degeneration, synovial inflammation, and abnormal bone remodeling. Early intervention is crucial to delay disease progression and reduce joint damage; however, effective and specific therapeutic targets are still lacking. Studies indicate that abnormal signaling crosstalk between synovium and cartilage is a core mechanism in knee osteoarthritis progression: inflammatory mediators released by synovial inflammation promote cartilage matrix degradation, while cartilage degradation products further exacerbate synovial inflammation, forming a vicious cycle that ultimately leads to an imbalance in cartilage anabolic and catabolic metabolism. Exosomes transmitted between synovium and cartilage play a dual role, both aggravating inflammation and potentially slowing knee osteoarthritis progression. Therefore, early targeted blockade of harmful signaling and precise promotion of protective signaling between synovium and cartilage represent potential strategies for intervention.
Synovial fluid exosomes, as key carriers of intercellular communication, play an important role in the pathological environment of knee osteoarthritis. They are secreted by various cells within the joint cavity (such as synoviocytes, chondrocytes, and immune cells) and are enriched with proteins, lipids, and nucleic acids (e.g., microRNAs), exhibiting high stability, tissue targeting, and bioactivity. Increasing evidence shows that synovial fluid exosomes deeply participate in bidirectional signaling between synoviocytes and chondrocytes through mechanisms such as inflammatory regulation, microRNA transfer, and extracellular matrix metabolism, exerting a decisive influence on joint microenvironment homeostasis. Given the central hub position of synovial fluid exosomes in synovial-cartilage signaling crosstalk, they are key research targets for exploring early pathological mechanisms and discovering novel diagnostic and therapeutic targets for knee osteoarthritis.
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WANG Yanfei, JIN Lianhai, LI Qingya, FU Yuanfei, TAN Huangsheng, DENG Pengwei, GAO Kun (2026). Synovial fluid exosome-mediated crosstalk between synoviocytes and chondrocytes in development and progression of knee osteoarthritis. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21499
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Frequently Asked Questions
What is the role of synovial fluid exosomes in knee osteoarthritis?
Synovial fluid exosomes mediate bidirectional signaling between synoviocytes and chondrocytes, playing a dual role in knee osteoarthritis progression. They can both exacerbate cartilage degeneration and synovial inflammation, and under certain conditions, exert protective effects, making them potential therapeutic targets.
How do synovial fluid exosomes affect the communication between synoviocytes and chondrocytes?
Synovial fluid exosomes carry proteins, lipids, and non-coding RNAs that are transferred between synoviocytes and chondrocytes, modulating gene expression and signaling pathways such as NF-κB, ferroptosis, and pyroptosis, thereby influencing the balance between cartilage matrix synthesis and degradation.
Can synovial fluid exosomes be used as biomarkers for knee osteoarthritis?
Yes, dynamic changes in exosomal non-coding RNAs (e.g., miR-140-5p, miR-21-5p, circ_0001236) have been shown to correlate with disease stage, suggesting that synovial fluid exosomes have potential as liquid biopsy biomarkers for early diagnosis and monitoring of knee osteoarthritis.
What are engineered exosomes and how might they be used in treating knee osteoarthritis?
Engineered exosomes are exosomes modified to enhance their therapeutic properties, such as enriching specific miRNAs (e.g., miR-140-3p, miR-26a-5p) to boost anti-inflammatory effects. They hold promise as targeted delivery vehicles for treating knee osteoarthritis by modulating the pathological signaling pathways.
What are the future research directions for synovial fluid exosomes in knee osteoarthritis?
Future research should focus on understanding the precise regulatory mechanisms of key non-coding RNAs in exosomes, determining whether the exosome-mediated communication is unidirectional or bidirectional and how it changes with disease stage, and improving the stability, distribution, and clearance of exosomes in the joint cavity to enhance their clinical feasibility as diagnostic and therapeutic tools.
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