The Role of Intra-Articular Delivery of BM-MSCs-Derived Exosomes in Improving Osteoarthritis: Implication of circYAP1/miRNA-21/TLR7 Axis.
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El-Din, Shimaa Saad
Aboulhoda, Basma Emad
Hassouna, Amira
Shakweer, Marwa M
Alghamdi, Mansour A
Essam, Doha
Essam, Mohamed
AlRakaf, Nawaf A
Elzahed, Hanaa M
Selmy, Asmaa
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Discovery Medicine
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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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MSCs-derived exosomes, circYAP1, inflammation, miRNA-21, osteoarthritis, 3206 Medical Biotechnology, 40 Engineering, 32 Biomedical and Clinical Sciences, 4003 Biomedical Engineering, Osteoarthritis, Aging, Biotechnology, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research, Arthritis, 5.2 Cellular and gene therapies, 5.1 Pharmaceuticals, Musculoskeletal
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Discov Med, ISSN: 1539-6509 (Print); 1944-7930 (Online), Discovery Medicine, 36(186), 1420-1429. doi: 10.24976/Discov.Med.202436186.132
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Copyright: © 2024 The Author(s). Published by Discovery Medicine. This is an open access article under the CC BY 4.0 license.
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Except where otherwise noted, this item's license is described as Copyright: © 2024 The Author(s). Published by Discovery Medicine. This is an open access article under the CC BY 4.0 license.