The Role of Extracellular Vesicles Derived from MicroRNA-146a–modified Mesenchymal Stem Cells in Modulating Inflammation in Experimental Glenohumeral Osteoarthritis

Baotao  Cao; Guangyuan  Liu; Kai  Gao; Wenqi  Fan; Wei  Zhao; Baibai  Wang

doi:10.18502/ijaai.v23i5.16752

Baotao Cao The Second Department of Joint, The Third Hospital of Shijiazhuang, Shijiazhuang, China
Guangyuan Liu The First Department of Joint, The Third Hospital of Shijiazhuang, Shijiazhuang, China
Kai Gao Traditional Chinese Medicine Orthopedics, The Third Hospital of Shijiazhuang, Shijiazhuang, China
Wenqi Fan Department of Pediatrics, Shijiazhuang Maternity Hospital, Shijiazhuang, China
Wei Zhao The First Department of Joint, The Third Hospital of Shijiazhuang, Shijiazhuang, China
Baibai Wang The Second Department of Joint, The Third Hospital of Shijiazhuang, Shijiazhuang, China

DOI: https://doi.org/10.18502/ijaai.v23i5.16752

Keywords: Exosome; Extracellular vesicles; Glenohumeral; Mesenchymal stem cells; Osteoarthritis

Abstract

Glenohumeral osteoarthritis (GOA) is characterized by chronic inflammation leading to joint damage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are promising therapies because of their immunomodulatory functions. The anti-inflammatory effects of EVs from human Adipose-derived MSCs (hADSCs) overexpressing microRNA (miR)-146a were investigated in experimental GOA in this study.

hADSCs were transfected with a mimic negative control or miR-146a mimics. GOA was induced in C57/Bl6j mice, and subsequently, the animals were treated intra-articularly with phosphate-buffered saline, miR-146a EVs, or miR-control EVs. The expression of miR-146a and its targeted cytokines interleukin (IL)-4, IL-10, tumor necrosis factor-alpha (TNF-α), IL-17, and interferon-gamma (IFN-γ) were analyzed in the spleen of mice by enzyme-linked immunosorbent assay and in the articular cartilage by real-time polymerase chain reaction.

miR-146a EVs showed enrichment of miR-146a. In GOA mice, miR-146a EV treatment significantly reduced expression levels of inflammatory cytokines IFN-γ, IL-17, and TNF-α and increased the anti-inflammatory cytokine IL-10 and IL-4 compared to controls. miR-146a EV treatment raised the anti-inflammatory cytokines and reduced the pro-inflammatory cytokines of the spleen in treated mice.

This study demonstrates that EVs derived from hADSCs overexpressing miR-146a have enhanced anti-inflammatory potential in GOA by modulating cytokine expression and production. EVs engineered with inflammation-related miRNAs could be a cell-free therapeutic approach for GOA.