Exosomes from human umbilical cord mesenchymal stem cells inhibit ROS production and cell apoptosis in human articular chondrocytes via the miR‐100‐5p/NOX4 axis

Abstract

Cyclic strain‐induced chondrocyte damage is actively involved in the pathogenesis of osteoarthritis and arthritis. MicroRNAs (miRNAs) carried by exosomes have been implicated in various diseases. However, the role of miR‐100‐5p in cyclic strain‐induced chondrocyte damage remains to be elucidated. miR‐100‐5p and NADPH oxidase 4 (NOX4) were silenced or overexpressed in human primary articular chondrocytes. PKH‐67 Dye was used to trace exosome endocytosis. Reactive oxygen species (ROS) production was monitored using DCFH‐DA. Cell apoptosis was measured using a flow cytometer. Quantitative RT‐PCR and Western blots were used to evaluate gene expression. Cyclic strain promoted ROS production and apoptosis in primary articular chondrocytes in a time‐dependent manner. HucMSCs‐derived exosomal miR‐100‐5p inhibited cyclic strain‐induced ROS production and apoptosis in primary articular chondrocytes. miR‐100‐5p directly targeted NOX4. Overexpressing NOX4 attenuated hucMSCs‐derived exosomes‐mediated protective effects in primary articular chondrocytes. Cyclic strain promotes ROS production and apoptosis in primary articular chondrocytes, which was abolished by hucMSCs‐derived exosomal miR‐100‐5p through its target NOX4. The findings highlight the importance of miR‐100‐5p/NOX4 axis in primary articular chondrocytes injury and provide new insights into therapeutic strategies for articular chondrocytes injury and osteoarthritis.

Breakthrough of extracellular vesicles in pathogenesis, diagnosis and treatment of osteoarthritis

“…Researchers found that exosomes from UMSCs could inhibit cyclic strain-induced ROS production and apoptosis, which is an important cause of chondrocyte injury in OA. This might owing to exosomal miR-100-5p inhibiting the expression of NOX4 [ 162 ]. UMSCs-sEVs could also promote the polarization of M2 macrophages and the expression of IL-10, thereby regulating the immune level of OA to slow down cartilage degradation.…”

Functional Mechanism of Mesenchymal Stem Cell-Derived Exosomes in Articular Cartilage Regeneration

“…MiR-31-5p protects oxidatively stressed EPCs from ER-stress-induced apoptosis and calcification [15]. Through miR-100-5p, derived from hucMSCs-EXOs, targeting NADPH oxidase 4 (NOX4), it can inhibit apoptosis and reactive oxygen species (ROS) production in primary articular chondrocytes [16].…”

Recent Therapeutic Strategies for Excessive Chondrocyte Death in Osteoarthritis: A Review

“…After BMSCs‐exo injection, the levels of inflammatory factors (TNFα, IL‐6) and chondrocyte apoptosis were reduced, the content of the main components of the ECM were increased in articular cartilage 135 . Moreover, numerous studies have shown great therapeutic potential of exosomes in inhibiting chondrocyte apoptosis with different mechanisms, and we present the details in Table 3 136–147 …”

“…135 Moreover, numerous studies have shown great therapeutic potential of exosomes in inhibiting chondrocyte apoptosis with different mechanisms, and we present the details in Table 3. [136][137][138][139][140][141][142][143][144][145][146][147] Platelet-rich plasma (PRP) has often been considered as a potential candidate for OA, showing an excellent ability to inhibit chondrocyte apoptosis, but the results of a recent clinical trial do not support that PRP can be used as a drug for OA. 148,149 Confusingly, recent studies have confirmed that both PRP and PRP-derived exosomes (PRP-exo) can inhibit chondrocyte apoptosis, which has led to controversy over the therapeutic effects of PRP and PRP-exo.…”