The Role of Intra-Articular Delivery of BM-MSCs-Derived Exosomes in Improving Osteoarthritis: Implication of circYAP1/ miRNA-21/ TLR7 Axis
Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently attracted great attention due to their crucial anti-inflammatory and regenerative properties. This work aims to examine the curative impact of intra-articular injection of BM-MSCs-derived exosomes in ameliorating osteoarthritis (OA) progression in rats and to explore the interaction between circular RNA of Yes-associated protein 1 ( circYAP1 ) and microRNA-21 ( miRNA-21 ) in the rat knee joints. Methodology: Gene expression circYAP1 , miRNA-21 , toll-like receptor-7 ( TLR7 ), aggrecan, and collagen type II were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the rat articular tissues. In addition, the Enzyme-linked immunosorbent assay (ELISA) technique was used to estimate the level of the inflammatory markers interleukin 4 (IL-4), interleukin 10 (IL-10), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α); and the oxidative markers glutathione (GSH), malondialdehyde (MDA) and total reactive oxygen species (ROS). Histopathological examination using Hematoxylin and Eosin (H&E) staining of the rat articular tissue was also performed along with an estimation of the articular cartilage thickness. Results: Our results showed that BM-MSCs-derived exosomes significantly elevated circYAP1 gene expression level ( p < 0.05) along with subsequent downregulation of miRNA-21 and TLR7 ( p < 0.05). These effects impacted the inflammatory milieu of rat articular surfaces, where there was a significant reduction ( p < 0.05) of the pro-inflammatory and oxidative markers with significantly increased production of the anti-inflammatory and antioxidative markers ( p < 0.05). Marked elevation in aggrecan and collagen type II gene expression was also found in the treated groups ( p < 0.05). Conclusion: Those data suggest that BM-MSCs-derived exosomes have a crucial role in mitigating OA symptoms and pathology progression and might be regarded as an effective as well as acceptable treatment option for OA.
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