Abstract
In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and extracellular vesicles (EVs) may play a major role in the efficacy of this treatment. Hypoxia can change the cargo and biological functions of MSC-derived EVs (MSC-EVs). The aim of the present study was to determine whether the effects of hypoxia-preconditioned MSC-EVs on OA cartilage repair are superior to normoxia-preconditioned MSC-EVs. By using in vitro and in vivo OA models, we verified that hypoxia-preconditioned MSC-EVs improved chondrocyte proliferation and migration and suppressed chondrocyte apoptosis to a greater extent than normoxia-preconditioned MSC-EVs. Furthermore, we found that hypoxia altered the microRNA expression in MSC-EVs and identified four differentially expressed microRNAs: hsa-miR-181c-5p, hsa-miR-18a-3p, hsa-miR-376a-5p, and hsa-miR-337-5p. Bioinformatics analysis revealed that hypoxic pretreatment may promote cartilage repair by stimulating chondrocyte proliferation and migration and suppressing chondrocyte apoptosis through the miRNA-18-3P/JAK/STAT or miRNA-181c-5p/MAPK signaling pathway. Therefore, hypoxia-preconditioned EVs may be a novel treatment for OA.
Highlights
Osteoarthritis (OA) is the most common joint disease and approximately 250 million people worldwide suffer from OA; large sums of money have been invested in OA research and treatment [1]
Recent studies have shown that the paracrine effects of mesenchymal stem cells (MSCs) are more important than differentiation in tissue repair, and more interest has been focused on extracellular vesicles (EVs) and their cargos [4]
P4 Bone Marrow MSCs (BMSCs) were observed under an optical microscope, and the image in Figure 1A shows that the cells displayed typical MSC morphology with a spindle-like shape
Summary
Osteoarthritis (OA) is the most common joint disease and approximately 250 million people worldwide suffer from OA; large sums of money have been invested in OA research and treatment [1]. The most important pathological change is articular cartilage damage. Except for pain relief and anti-inflammatory effects, none of these drugs can prevent or reverse cartilage damage in OA. MSCs have the potential for directed differentiation into multiple lineages, including mesenchymal and non-mesenchymal lineages [3]. In addition to their differentiation abilities, MSCs have a strong paracrine ability and can secrete a large number of molecules or vesicles. Recent studies have shown that the paracrine effects of MSCs are more important than differentiation in tissue repair, and more interest has been focused on extracellular vesicles (EVs) and their cargos [4]
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