Synovial fluid-derived extracellular vesicles modulate joint cell function in osteoarthritis.

Abstract

Introduction: Osteoarthritis (OA) is an age-related joint disease characterized by chronic inflammation and extracellular matrix degradation. Extracellular vesicles (EVs) in synovial fluid (SF) may modulate intercellular communication and influence disease progression.

Material and methods: SF, cartilage, and synovial tissue were collected from knee OA patients (n = 68). SF-derived EVs (SF-EVs) were isolated by size exclusion chromatography and characterized by transmission electron microscopy (TEM), tunable resistive pulse sensing (qNano), and ELISA analysis of EV-associated markers (CD9, CD81, TSG101, and PDCD6IP) and the negative marker calnexin. In vitro experiments were performed using primary synoviocytes and chondrocytes stimulated with interleukin (IL)-1β in the presence or absence of SF-EVs. Inflammatory and catabolic markers were measured.

Results: SF-EVs (∼261 nm; ∼7 × 10⁸ particles/mL) expressed canonical EV markers. In synoviocytes, SF-EVs reduced IL-1β-induced proliferation and decreased IL-6 and MMP-3 while increasing hyaluronic acid (HA). In chondrocytes, SF-EVs reduced IL-6 and MMP-13 and enhanced HA and IL-1Ra production, with sustained effects over time.

Conclusion: These findings suggest that SF-EVs can modulate inflammatory and matrix-related responses in joint-resident cells under IL-1β-induced inflammatory conditions. Their distinct effects on synoviocytes and chondrocytes highlight the potential role of SF-EVs in regulating cell-specific responses within the osteoarthritic joint and warrant further investigation into their contribution to OA pathophysiology.