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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Impacts of mesenchymal stem cells and hyaluronic acid on inflammatory indicators and antioxidant defense in experimental ankle osteoarthritis
Usama Ismaeil Hagag, Fatma Mohamed Halfaya, Hessah Mohammed Al-Muzafar, Suhailah Saud Al-Jameel, Kamal Adel Amin, Wael Abou El-Kheir, Emad A Mahdi, Gamal Abdel-Nasser Ragab Hassan, Osama Mohamed Ahmed
Usama Ismaeil Hagag, Department of Surgery, Beni-Suef University, Beni Suef 62111, Egypt
Fatma Mohamed Halfaya, Department of Surgery, Anesthesiology and Radiology, Beni-Suef University, Beni Suef 62111, Egypt
Hessah Mohammed Al-Muzafar, Suhailah Saud Al-Jameel, Department of Chemistry, College of Science, Basic and Applied Scientific Research Center, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
Kamal Adel Amin, Department of Chemistry, Biochemistry, College of Science, Basic and Applied Scientific Research Center (BASRC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
Wael Abou El-Kheir, Department of Immunology, Military Medical Academy, Cairo 11511, Al Qāhirah, Egypt
Emad A Mahdi, Department of Pathology, Beni-Suef University, Beni Suef 62111, Egypt
Gamal Abdel-Nasser Ragab Hassan, Department of Surgery, Anesthesiology and Radiology, Faculty of Veterinary Medicine, Beni-Suef University, Beni Suef 62521, Egypt
Osama Mohamed Ahmed, Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62521, Egypt
Author contributions: Hassan GANR, Abou El-Kheir W, Hagag UI, Al-Muzafar HM, Al-Jameel SS, Amin KA, and Ahmed OM conceptualized and designed the study; Halfaya FM, Abou El-Kheir W, Mahdi EA , Al-Muzafar HM, Al-Jameel SS, Amin KA, Hagag UI, and Ahmed OM contributed to the methodology, investigation, and supervision; Halfaya FM and Ahmed OM performed the formal and statistical analyses; Abou El-Kheir W, Halfaya FM, Ahmed OM, Mahdi EA, Al-Muzafar HM, Al-Jameel SS, and Amin KA obtained the support resources; Halfaya FM, Ahmed OM, Mahdi EA, Muzafar HM, Al-Jameel SS, and Amin KA wrote and edited the original draft; All authors reviewed the data and approved the final manuscript.
Institutional animal care and use committee statement: All animal approaches and the experiment are in harmony with the standard guidelines of the Institutional Animal Care and Use Committee, Beni-Suef University, Beni-Suef, Egypt, No. BSU/020-107.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Kamal Adel Amin, PhD, Full Professor, Department of Chemistry, Bio
chemistry, College of Science, Basic and Applied Scientific Research Center, Imam Abdu
lrahman Bin Faisal University, PO Box 1982, Dammam 31441, Saudi Arabia.
kaothman@iau.edu.sa
Received: May 7, 2024
Revised: August 13, 2024
Accepted: October 9, 2024
Published online: November 18, 2024
Processing time: 191 Days and 14.4 Hours
BACKGROUND
No effective treatment guarantees full recovery from osteoarthritis (OA), and few therapies have disadvantages.
AIM
To determine if bone marrow mesenchymal stem cells (BMMSCs) and hyaluronic acid (HA) treat ankle OA in Wistar rats.
METHODS
BMMSCs were characterized using flow cytometry with detection of surface markers [cluster of differentiation 90 (CD90), CD105, CD34, and CD45]. Fifty male Wistar rats were divided into five groups of 10 rats each: Group I, saline into the right tibiotarsal joint for 2 days; Group II, monosodium iodate (MIA) into the same joint; Groups III, MIA + BMMSCs; Group IV, MIA + HA; and Group V, MIA + BMMSCs + HA. BMMSCs (1 × 106 cells/rat), HA (75 µg/rat), and BMMSCs (1 × 106 cells/rat) alongside HA (75 µg/rat) were injected intra-articularly into the tibiotarsal joint of the right hind leg at the end of weeks 2, 3, and 4 after the MIA injection.
RESULTS
The elevated right hind leg circumference values in the paw and arthritis clinical score of osteoarthritic rats were significantly ameliorated at weeks 4, 5, and 6. Lipid peroxide significantly increased in the serum of osteoarthritic rats, whereas reduced serum glutathione and glutathione transferase levels were decreased. BMMSCs and HA significantly improved OA. The significantly elevated ankle matrix metalloproteinase 13 (MMP-13) mRNA and transforming growth factor beta 1 (TGF-β1) protein expression, and tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17) serum levels in osteoarthritic rats were significantly downregulated by BMMSCs and HA. The effects of BMMSCs and HA on serum TNF-α and IL-17 were more potent than their combination. The lowered serum IL-4 levels in osteoarthritic rats were significantly upregulated by BMMSCs and HA. Additionally, BMMSCs and HA caused a steady decrease in joint injury and cartilage degradation.
CONCLUSION
BMMSCs and/or HA have anti-arthritic effects mediated by antioxidant and anti-inflammatory effects on MIA-induced OA. MMP-13 and TGF-β1 expression improves BMMSCs and/or HA effects on OA in Wistar rats.
Core Tip: We determined the effectiveness of bone marrow mesenchymal stem cells (BMMSCs) and/or hyaluronic acid (HA) in treating ankle osteoarthritis (OA). BMMSCs were characterized by flow cytometry. Lipid peroxidation, matrix metalloproteinase 13 (MMP-13) mRNA, transforming growth factor beta 1 (TGF-β1) protein expression, and tumor necrosis factor alpha and interleukin-17 serum levels significantly increased in osteoarthritic rats, while antioxidant serum glutathione and glutathione transferase levels decreased. Treatment of osteoarthritic rats with BMMSCs and HA improved these changes. BMMSCs and/or HA have anti-arthritic effects mediated by increased antioxidant and anti-inflammatory effects and suppression of MMP-13 and TGF-β1 expression in Wistar rats with OA.
