The Role of Intra-Articular Delivery of BM-MSCs-Derived Exosomes in Improving Osteoarthritis: Implication of <i>circYAP1</i>/<i>miRNA-21</i>/<i>TLR7</i> Axis

Abstract

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 (<i>circYAP1</i>) and microRNA-21 (<i>miRNA-21</i>) in the rat knee joints. Methodology: Gene expression <i>circYAP1</i>, <i>miRNA-21</i>, toll-like receptor-7 (<i>TLR7</i>), 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 <i>circYAP1</i> gene expression level (<i>p</i> < 0.05) along with subsequent downregulation of <i>miRNA-21</i> and <i>TLR7</i> (<i>p</i> < 0.05). These effects impacted the inflammatory milieu of rat articular surfaces, where there was a significant reduction (<i>p</i> < 0.05) of the pro-inflammatory and oxidative markers with significantly increased production of the anti-inflammatory and antioxidative markers (<i>p</i> < 0.05). Marked elevation in aggrecan and collagen type II gene expression was also found in the treated groups (<i>p</i> < 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.