Ameliorative effects of undifferentiated and differentiated BM-MSCs in MIA-induced osteoarthritic Wistar rats: roles of NF-κB and MMPs signaling pathways.
Ablaa S Saleh, Mohammed Abdel-Gabbar, Hala Gabr, Anwar Shams, Shadi Tamur, Emad A Mahdi, Osama M Ahmed
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引用次数: 0
Abstract
Objectives: Osteoarthritis (OA) is a degenerative joint condition that is persistent. OA affects millions of people throughout the world. Both people and society are heavily economically burdened by osteoarthritis. There is currently no medication that can structurally alter the OA processes or stop the disease from progressing. Stem cells have the potential to revolutionize medicine due to their capacity to differentiate into chondrocytes, capacity to heal tissues and organs including osteoarthritic joints, and immunomodulatory capabilities. Therefore, the goal of the current investigation was to determine how bone marrow-derived mesenchymal stem cells (BM-MSCs) and chondrogenic differentiated mesenchymal stem cells (CD-MSCs) affected the treatment of OA in rats with monosodium iodoacetate (MIA)-induced osteoarthritis.
Methods: Male Wistar rats were injected three times with MIA (1 mg)/100 µL isotonic saline to induce osteoarthritis in the ankle joint of the right hind leg. Following the MIA injection, the osteoarthritic rats were given weekly treatments of 1 × 106 BM-MSCs and CD-MSCs into the tail vein for three weeks.
Results: The obtained results showed that in osteoarthritic rats, BM-MSCs and CD-MSCs dramatically decreased ankle diameter measurements, decreased oxidized glutathione (GSSG) level, and boosted glutathione peroxidase (GPx) and glutathione reductase (GR) activities. Additionally, in rats with MIA-induced OA, BM-MSCs and CD-MSCs dramatically boosted interleukin-10 (IL-10) serum levels while considerably decreasing serum anticitrullinated protein antibodies (ACPA), tumour necrosis factor-α (TNF-α), and interleukin-17 (IL-17) levels as well as ankle transforming growth factor-β1 (TGF-β1) expression. Analysis of histology, immunohistochemistry, and western blots in osteoarthritic joints showed that cartilage breakdown and joint inflammation gradually decreased over time.
Conclusions: It is possible to conclude from these results that BM-MSCs and CD-MSCs have anti-arthritic potential in MIA-induced OA, which may be mediated via inhibitory effects on oxidative stress, MMPs and inflammation through suppressing the NF-κB pathway. In osteoarthritis, using CD-MSCs as a treatment is more beneficial therapeutically than using BM-MSCs.
期刊介绍：
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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