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

doi:10.5312/wjo.v15.i11.1056

Impacts of mesenchymal stem cells and hyaluronic acid on inflammatory indicators and antioxidant defense in experimental ankle osteoarthritis

World J Orthop. 2024 Nov 18;15(11):1056-1074. doi: 10.5312/wjo.v15.i11.1056.

Authors

Usama Ismaeil Hagag¹, Fatma Mohamed Halfaya², Hessah Mohammed Al-Muzafar³, Suhailah Saud Al-Jameel³, Kamal Adel Amin⁴, Wael Abou El-Kheir⁵, Emad A Mahdi⁶, Gamal Abdel-Nasser Ragab Hassan⁷, Osama Mohamed Ahmed⁸

Affiliations

¹ Department of Surgery, Beni-Suef University, Beni Suef 62111, Egypt.
² Department of Surgery, Anesthesiology and Radiology, Beni-Suef University, Beni Suef 62111, Egypt.
³ Department of Chemistry, College of Science, Basic and Applied Scientific Research Center, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
⁴ Department of Chemistry, Biochemistry, College of Science, Basic and Applied Scientific Research Center (BASRC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia. kaothman@iau.edu.sa.
⁵ Department of Immunology, Military Medical Academy, Cairo 11511, Al Qāhirah, Egypt.
⁶ Department of Pathology, Beni-Suef University, Beni Suef 62111, Egypt.
⁷ Department of Surgery, Anesthesiology and Radiology, Faculty of Veterinary Medicine, Beni-Suef University, Beni Suef 62521, Egypt.
⁸ Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62521, Egypt.

Abstract

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.

Keywords: Anti-inflammatory; Antioxidant; Bone marrow mesenchymal stem cells; Hyaluronic acid; Osteoarthritis.