Evaluation of Serum Biomarkers After Intra-articular Injection of Rat Bone Marrow-derived Mesenchymal Stem Cells in a Rat Model of Knee Osteoarthritis

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Nov 18

PMID 39553645

Authors

Abdulwahab Noorwali

Fadwa Aljoud

Amani Alghamdi

Noora Sattami

Taghreed Bashah

Abdulsalam Noorwali

Peter Natesan Pushparaj

Kalamegam Gauthaman

Affiliations

Soon will be listed here.

Abstract

Background: Osteoarthritis (OA) is a prevalent joint disorder characterized by joint pain, functional impairment, and disability. The current study investigated the therapeutic effects of intra-articular injection of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) in rats with knee OA.

Methods: Fourty five male Wistar rats were randomly divided into three groups (A-C) and received either an intra-articular injection of normal saline (NS) or rBM-MSCs. The normal control group (A, n = 15) received NS, the OA control group (B, n = 15) received NS, and the OA treated group (C, n = 15) received rBM-MSCs (0.5 × 10 cells in 25 μL NS). Knee OA was induced using monosodium iodoacetate (MIA). rBM-MSCs were sourced from female Wistar rats and their stem cells were characterized using flow cytometry. Histomorphometric analyses were performed on knee sections from both normal and OA knee. Serum biomarkers, including hyaluronic acid (HA), cross-linked N-telopeptide of type I collagen-1 (NTX-1), NGF, calcitonin gene-related peptide (CGRP), matrix metalloproteinase-3 (MMP-3), oligomeric cartilage matrix protein COMP, interleukin-6 (IL-6), and soluble IL-6 receptor (sIL-6R), were analyzed using ELISA kits. Ingenuity Pathway Analysis (IPA) was used to determine the genes regulated by MSCs in OA, and the protective mechanisms were determined using the Molecular Activity Predictor (MAP).

Results: rBM-MSCs were positive for CD29 and CD90 and negative for CD45 surface markers. OA biomarkers were significantly elevated in the untreated OA group but decreased after treatment with intra-articular MSCs. The OA group treated with MSCs showed significant repair of the damaged cartilage compared to the control group.

Conclusions: Cartilage damage leads to an increase in inflammatory cytokine levels and is associated with an increase in serum biomarkers related to cartilage degradation. Intra-articular administration of MSCs showed beneficial effects, including regeneration of damaged cartilage and a reduction in inflammation-related serum biomarker levels.

References

Guzman R, Evans M, Bove S, Morenko B, Kilgore K . Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: an animal model of osteoarthritis. Toxicol Pathol. 2003; 31(6):619-24. DOI: 10.1080/01926230390241800. View

Hong Y, Xu H, Yang Y, Zhou S, Jin A, Huang X . Isolation and Cultivation of Mandibular Bone Marrow Mesenchymal Stem Cells in Rats. J Vis Exp. 2020; (162). DOI: 10.3791/61532. View

Singer N, Caplan A . Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2010; 6:457-78. DOI: 10.1146/annurev-pathol-011110-130230. View

Lee K, Hui J, Song I, Ardany L, Lee E . Injectable mesenchymal stem cell therapy for large cartilage defects--a porcine model. Stem Cells. 2007; 25(11):2964-71. DOI: 10.1634/stemcells.2006-0311. View

Iannone F, De Bari C, DellAccio F, Covelli M, Patella V, Lo Bianco G . Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes. Rheumatology (Oxford). 2002; 41(12):1413-8. DOI: 10.1093/rheumatology/41.12.1413. View

Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L . Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy - a review. BMC Musculoskelet Disord. 2016; 17:230. PMC: 4880954. DOI: 10.1186/s12891-016-1085-9. View

Pavelka K, Forejtova S, Olejarova M, Gatterova J, Senolt L, Spacek P . Hyaluronic acid levels may have predictive value for the progression of knee osteoarthritis. Osteoarthritis Cartilage. 2004; 12(4):277-83. DOI: 10.1016/j.joca.2004.01.001. View

Bullock C, Wookey P, Bennett A, Mobasheri A, Dickerson I, Kelly S . Peripheral calcitonin gene-related peptide receptor activation and mechanical sensitization of the joint in rat models of osteoarthritis pain. Arthritis Rheumatol. 2014; 66(8):2188-200. PMC: 4314689. DOI: 10.1002/art.38656. View

Stoppiello L, Mapp P, Wilson D, Hill R, Scammell B, Walsh D . Structural associations of symptomatic knee osteoarthritis. Arthritis Rheumatol. 2014; 66(11):3018-27. PMC: 4309484. DOI: 10.1002/art.38778. View

10.

Murphy J, Fink D, Hunziker E, Barry F . Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003; 48(12):3464-74. DOI: 10.1002/art.11365. View

11.

Verma P, Dalal K . Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: a novel diagnostic and prognostic biomarker. J Orthop Res. 2013; 31(7):999-1006. DOI: 10.1002/jor.22324. View

12.

Rukwied R, Mayer A, Kluschina O, Obreja O, Schley M, Schmelz M . NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity in human skin. Pain. 2009; 148(3):407-413. DOI: 10.1016/j.pain.2009.11.022. View

13.

Gardiner B, Woodhouse F, Besier T, Grodzinsky A, Lloyd D, Zhang L . Predicting Knee Osteoarthritis. Ann Biomed Eng. 2015; 44(1):222-33. PMC: 4690844. DOI: 10.1007/s10439-015-1393-5. View

14.

Atley L, Mort J, Lalumiere M, Eyre D . Proteolysis of human bone collagen by cathepsin K: characterization of the cleavage sites generating by cross-linked N-telopeptide neoepitope. Bone. 2000; 26(3):241-7. DOI: 10.1016/s8756-3282(99)00270-7. View

15.

Otis C, Gervais J, Guillot M, Gervais J, Gauvin D, Pethel C . Concurrent validity of different functional and neuroproteomic pain assessment methods in the rat osteoarthritis monosodium iodoacetate (MIA) model. Arthritis Res Ther. 2016; 18:150. PMC: 4918125. DOI: 10.1186/s13075-016-1047-5. View

16.

Hunter D, Bierma-Zeinstra S . Osteoarthritis. Lancet. 2019; 393(10182):1745-1759. DOI: 10.1016/S0140-6736(19)30417-9. View

17.

Chen D, Shen J, Zhao W, Wang T, Han L, Hamilton J . Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res. 2017; 5:16044. PMC: 5240031. DOI: 10.1038/boneres.2016.44. View

18.

Frisbie D, Kisiday J, Kawcak C, Werpy N, McIlwraith C . Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. J Orthop Res. 2009; 27(12):1675-80. DOI: 10.1002/jor.20933. View

19.

Emadedin M, Aghdami N, Taghiyar L, Fazeli R, Moghadasali R, Jahangir S . Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012; 15(7):422-8. DOI: 012157/AIM.0010. View

20.

Miyamoto S, Nakamura J, Ohtori S, Orita S, Omae T, Nakajima T . Intra-articular injection of mono-iodoacetate induces osteoarthritis of the hip in rats. BMC Musculoskelet Disord. 2016; 17:132. PMC: 4797112. DOI: 10.1186/s12891-016-0985-z. View