Background/Purpose: Osteoarthritis (OA) is an age-related musculoskeletal disease and the most common form of arthritis characterized by low grade synovial inflammation and articular cartilage degeneration. Many different cell types have been implicated in the pathogenesis of OA and interplay between these cells contribute to the dynamic events associated with disease. Recently, extracellular vesicles (EVs) have emerged as mediators of intercellular communication. Being carriers of proteins, genetic information and metalloproteinases, their involvement in many diseases has now been established. There is however very little known about the pathophysiological role of EVs in musculoskeletal diseases. In this study, we investigated the effect of plasma EVs from OA patients during chondrogenic differentiation of mesenchymal stem cells (MSCs).

Methods: Plasma-derived extracellular vesicles (pEVs) were isolated from plasma of OA patients and age-matched healthy controls using size-exclusion chromatography. EV containing fractions were characterized according to ISEV guidelines [1]. Pelleted MSCs were stimulated with TGF-β and BMP-2 to induce chondrogenic differentiation, either in the presence of pEVs isolated from OA patients or healthy controls. After 8 days, RNA was isolated and RT-qPCR was performed to determine the gene expression profiles.

Results: No significant difference was observed in particle concentration, size or protein concentration between OA patients and age-matched controls. In the presence of pEVs from OA patients MSC-derived chondrocytes showed a significant increase in the expression of MMP13 (6.1-fold), RUNX2 (1.9-fold) and RANKL (2.3-fold), compared to pEVs from healthy controls. A trend towards higher ADAMTS5 expression (2.5-fold, p=0.0685) with OA pEVs was also observed. Additionally, we found significantly higher expression of WISP1 (24-fold), suggesting activation of Wnt signaling. All other proinflammatory genes tested were not significantly different between the two groups.

Conclusion: A previous study [2] has shown that EVs released from IL-1β stimulated synovial fibroblasts can induce osteoarthritic changes in articular chondrocytes. Here, we show direct evidence that circulating pEVs from OA patients can enhance OA-related genes, like MMP13, in MSC-derived chondrocytes. The expression profile found suggest the presence of Wnt-proteins on pEVs from OA patients, which are known to be involved in cartilage development and we previously have shown that WISP-1 expression is a feature of experimental and human OA [3].

[1] J. Lötvall, et al. Journal of extracellular vesicles (2014).

[2] T. Kato, et al. Arthritis Research & Therapy (2014).

[3] A. B. Blom, et al. Arthritis & Rheumatology (2009).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/chondrocytes-derived-from-mesenchymal-stem-cells-differentiated-in-the-presence-of-plasma-derived-extracellular-vesicles-from-osteoarthritic-patients-express-disease-related-genes/