Association between cytokines and exosomes in synovial fluid of individuals with knee osteoarthritis

Abstract

Background: Cytokines in synovial fluid (SF) play a crucial role in knee osteoarthritis (KOA). Exosomes are nanovesicles that are abundant in SF and carry a large quantity of signaling molecules. The purpose of this study was to evaluate the cytokine profiles of SF-derived exosomes and try to explore its biological function.

Methods: Twenty-four KOA patients who were scheduled for their first intra-articular injection or knee replacement surgery were enrolled and divided into the KL1–2 group and the KL3–4 group according to the Kellgren and Lawrence (KL) classification. SF was collected from the patient’s knee for the isolation of exosomes. A multiplex cytokine assay was performed to detect the 21 cytokines in the exosomes. The SF derived-exosomes were exposed to PBMCs and chondrocytes to assess their immunomodulatory potential.

Results: Exosomes were successfully extracted from the SF, with an average diameter of 92 nm. Most cytokines were detectable in the SF-derived exosomes. Twelve inflammatory cytokines and eight chemokines were elevated in the exosomes of the KL3–4 group compared to that of the KL1–2 group (p < .05). A higher number of PBMCs were chemo attracted and the proliferation of chondrocytes was restrained by the SF-derived exosomes from the KL3–4 group in comparison with the KL1–2 group (p < .05).

Conclusion: Our data indicated that most cytokines in SF are not only in a free form but also associated with and enriched in exosomes. Exosomes from end-stage KOA patients have a higher level of cytokines, especially chemokines, in comparison with the cytokine profiles of the soluble SF. SF-derived exosomes recruit inflammatory cells and inhibit cartilage proliferation, thus promoting joint degeneration. These data provide a new perspective for understanding the changes in the inner environment of KOA.

Keywords:

• Knee osteoarthritis
• cytokines
• chemokines
• exosomes

Acknowledgements

Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent: Informed consent was obtained from all individual participants included in the study.

Conflict of interest

None.

Additional information

Funding

This study was funded by grants of Sanming Project of Medicine in Shenzhen (No. SZSM201812066), and NSFC-Guangdong Joint Foundation of China (No. U1601225), Guangdong Provincial Science and Technology Projects (No. 2016A020216015).