The Effect of Mesenchymal Stem Cell Wharton's Jelly on Matrix Metalloproteinase-1 and Interleukin-4 Levels in Osteoarthritis Rat Model

Endrinaldi Endrinaldi; Eryati Darwin; Nasrul Zubir; Gusti Revilla

doi:10.3889/oamjms.2019.152

Authors

Endrinaldi Endrinaldi Postgraduate Biomedical Science, Faculty of Medicine, Andalas University, Padang, Indonesia; Department of Chemistry, Faculty of Medicine, Andalas University, Padang, Indonesia
Eryati Darwin Department of Histology, Faculty of Medicine, Andalas University, Padang, Indonesia
Nasrul Zubir Department of Internal Medicine, Faculty of Medicine, Andalas University, Padang, Indonesia
Gusti Revilla Department of Anatomy, Faculty of Medicine, Andalas University, Padang, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2019.152

Keywords:

Matrix Metalloproteinase-1, Mesenchymal Stem Cell Wharton Jelly, Interleukin-4, Osteoarthritis

Abstract

BACKGROUND: Osteoarthritis (OA) is generally considered a degenerative joint disease caused by biomechanical changes and the ageing process. In OA pathogenesis, the development of OA is thought to be regulated largely by excess matrix metalloproteinase (MMP), which contributes to the degradation of extracellular matrices such as MMP-1 and Interleukin-4.

AIM: This study aims to prove the influence of Mesenchymal Stem Cell Wharton Jelly on decreasing MMP-1 levels and increasing IL-4 which is a specific target as a target component in cases of osteoarthritis in vivo.

MATERIAL AND METHODS: This research is an experimental study with the design of Post-Test-Only Control Group Design. The sample consisted of 16 OA rats as a control group and 16 OA rats treated with MSC-WJ as a treatment group. OA induction is done by injection of monosodium iodoacetate (MIA) into the intra-articular right knee. Giving MSC-WJ is done in the third week after MIA induction. The serum MMP-1 and IL-4 levels were measured after 3 weeks treated with MSC-WJ using the ELISA method. The statistical test used is an independent t-test. The value of p < 0.05 was said to be statistically significant.

RESULTS: The result showed that serum MMP-1 levels were higher in the group treated with MSC-WJ than in the control group (p < 0.05). Serum IL-4 levels were higher in the group treated with MSC-WJ than in the control group (p < 0.05).

CONCLUSION: This study concluded that MSC-WJ increased MMP-1 levels and IL-4 levels in serum OA rats. MSC-WJ showed a negative effect on MMP-1 in the serum of OA rats.

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References

Poole A.R. Cartilage in health and disease. In: Arthritis and Allied Conditions: A Textbook of rheumatology.14th Edition. Edited by Koopman, W.J., Williams & Wilkins, Baltimore, 2000.

Yan Z, Xiong J, Zhao C, Qin C, He. 2015. Decreasing cartilage damage in a rat model of osteoarthritis by intra-articular injection of deoxycholic acid. Int J Clin Exp Med. 2015; 8(6):9038-9045. PMid:26309557 PMCid:PMC4538145

Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases. Arthritis research & therapy. 2009; 11(3):224. https://doi.org/10.1186/ar2592 PMid:19519926 PMCid:PMC2714092

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. science. 1999; 284(5411):143-7. https://doi.org/10.1126/science.284.5411.143 PMid:10102814

Chen L, Tredget EE, Wu PY, Wu Y. Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PloS one. 2008; 3(4):e1886. https://doi.org/10.1371/journal.pone.0001886 PMid:18382669 PMCid:PMC2270908

Bove SE, Calcaterra SL, Brooker RM, Huber CM, Guzman RE, Juneau PL, Schrier DJ, Kilgore KS. Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthritis and cartilage. 2003; 11(11):821-30. https://doi.org/10.1016/S1063-4584(03)00163-8

Kelly S, Dobson KL, Harris J. Spinal nociceptive reflexes are sensitized in the monosodium iodoacetate model of osteoarthritis pain in the rat. Osteoarthritis and cartilage. 2013; 21(9):1327-35. https://doi.org/10.1016/j.joca.2013.07.002 PMid:23973147

Kim JS, Kroin JS, Buvanendran A, Li X, Van Wijnen AJ, Tuman KJ, Im HJ. Characterization of a new animal model for evaluation and treatment of back pain due to lumbar facet joint osteoarthritis. Arthritis & Rheumatism. 2011; 63(10):2966-73. https://doi.org/10.1002/art.30487 PMid:21953085 PMCid:PMC3187574

Stracke JO, Fosang AJ, Last K, Mercuri FA, PendÃ¡s AM, Llano E, Perris R, Di Cesare PE, Murphy G, KnÃ¤uper V. Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP). FEBS letters. 2000; 478(1-2):52-6. https://doi.org/10.1016/S0014-5793(00)01819-6

DeGroot J, Verzijl N, Marion JG, Wenting-Van Wijk, Bank RA, Lafeber FP, Bijlsma WJ, TeKoppele JM. Age-Related Decrease in Susceptibility of Human Articular Cartilage to Matrix Metalloproteinaseâ€“Mediated Degradation. Arthritis Rheum. 2001; 44(11): 2562â€“2571. https://doi.org/10.1002/1529-0131(200111)44:11<2562::AID-ART437>3.0.CO;2-1

Goldring MB. The role of the chondrocyte in osteoarthritis. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 2000; 43(9):1916-26. https://doi.org/10.1002/1529-0131(200009)43:9<1916::AID-ANR2>3.0.CO;2-I

van Buul GM, Siebelt M, Leijs MJ, Bos PK, Waarsing JH, Kops N, Weinans H, Verhaar JA, Bernsen MR, van Osch GJ. Mesenchymal stem cells reduce pain but not degenerative changes in a monoâ€iodoacetate rat model of osteoarthritis. Journal of Orthopaedic Research. 2014; 32(9):1167-74. https://doi.org/10.1002/jor.22650 PMid:24839120

Janusz MJ, Hookfin EB, Heitmeyer SA, Woessner JF, Freemont AJ, Hoyland JA, Brown KK, Hsieh LC, Almstead NG, De B, Natchus MG. Moderation of iodoacetate-induced experimental osteoarthritis in rats by matrix metalloproteinase inhibitors. Osteoarthritis and Cartilage. 2001; 9(8):751-60. https://doi.org/10.1053/joca.2001.0472 PMid:11795995

Stracke JO, Fosang AJ, Last K, Mercuri FA, PendÃ¡s AM, Llano E, Perris R, Di Cesare PE, Murphy G, KnÃ¤uper V. Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP). FEBS letters. 2000; 478(1-2):52-6. https://doi.org/10.1016/S0014-5793(00)01819-6

DeGroot J, Verzijl N, Marion J. G. Wenting-Van Wijk, Bank RA., Lafeber FP, Bijlsma WJ, and TeKoppele JM. Age-Related Decrease in Susceptibility of Human Articular Cartilage to Matrix Metalloproteinaseâ€“Mediated Degradation. Arthritis Rheum. 2001; 44(11):2562â€“2571. https://doi.org/10.1002/1529-0131(200111)44:11<2562::AID-ART437>3.0.CO;2-1

Almalki SG, Agrawal DK. Effects of matrix metalloproteinases on the fate of mesenchymal stem cells. Stem cell research & therapy. 2016; 7(1):129. https://doi.org/10.1186/s13287-016-0393-1 PMid:27612636 PMCid:PMC5016871

Fahmi H, Pelletier J.-P, Di Battista J. A, CheungÃœ H. S, Fernandes J. C and Martel-Pelletier J. Peroxisome proliferator-activated receptor gamma activators inhibit MMP-1 production in human synovial fibroblasts likely by reducing the binding of the activator protein 1. J. OsteoArthritis Research Society Int. 2002; 10(2):100-108. https://doi.org/10.1053/joca.2001.0485 PMid:11869069

Tetlow LC, Adlam DJ, Woolley DE. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis & Rheumatism. 2001; 44(3):585-94. https://doi.org/10.1002/1529-0131(200103)44:3<585::AID-ANR107>3.0.CO;2-C

Saulnier N, Viguier E, Perrier-Groult E, Chenu C, Pillet E, Roger T, Maddens S, Boulocher C. Intra-articular administration of xenogeneic neonatal mesenchymal stromal cells early after meniscal injury down-regulates metalloproteinase gene expression in synovium and prevents cartilage degradation in a rabbit model of osteoarthritis. Osteoarthritis and cartilage. 2015; 23(1):122-33. https://doi.org/10.1016/j.joca.2014.09.007 PMid:25219668

Zhao S, Zhao Y, Guo J, Fei C, Zheng Q, Li X, Chang C. Downregulation of MMP1 in MDS-derived mesenchymal stromal cells reduces the capacity to restrict MDS cell proliferation. Scientific reports. 2016; 7:43849. https://doi.org/10.1038/srep43849 PMid:28262842 PMCid:PMC5338350

Ho IA, Chan KY, Ng WH, Guo CM, Hui KM, Cheang P, Lam PY. Matrix metalloproteinase 1 is necessary for the migration of human bone marrowâ€derived mesenchymal stem cells toward human glioma. Stem Cells. 2009; 27(6):1366-75. https://doi.org/10.1002/stem.50 PMid:19489099 PMCid:PMC2771102

Voronkina IV, Smagina LV, Krylova TA, Musorina AS, Poljanskaya GG. Analysis of matrix metalloproteinase activity during differentiation of mesenchymal stem cells isolated from different tissues of one donor. Cell and Tissue Biology. 2017; 11(2):95-103. https://doi.org/10.1134/S1990519X17020092

Ponte AL, Marais E, Gallay N, LangonnÃ© A, Delorme B, HÃ©rault O, Charbord P, Domenech J. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem cells. 2007; 25(7):1737-45. https://doi.org/10.1634/stemcells.2007-0054 PMid:17395768

Hui W, Barksby HE, Young DA, Cawston TE, Mckie N, Rowan AD. Oncostatin M in combination with tumour necrosis factor Î± induces a chondrocyte membrane associated aggrecanase that is distinct from ADAMTS aggrecanase-1 or -2. Annals of the rheumatic diseases. 2005; 64(11):1624-32. https://doi.org/10.1136/ard.2004.028191 PMid:15883123 PMCid:PMC1755260

Sze SK, de Kleijn DP, Lai RC, Tan EK, Zhao H, Yeo KS, Low TY, Lian Q, Lee CN, Mitchell W, El Oakley RM. Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells. Molecular & Cellular Proteomics. 2007; 6(10):1680-9. https://doi.org/10.1074/mcp.M600393-MCP200 PMid:17565974

Skalnikova H, Motlik J, Gadher SJ, Kovarova H. Mapping of the secretome of primary isolates of mammalian cells, stem cells and derived cell lines. Proteomics. 2011; 11(4):691-708. https://doi.org/10.1002/pmic.201000402 PMid:21241017

Kay AG, Long G, Tyler G, Stefan A, Broadfoot SJ, Piccinini AM, Middleton J, Kehoe O. Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis. Scientific reports. 2017; 7(1):18019. https://doi.org/10.1038/s41598-017-18144-w PMid:29269885 PMCid:PMC5740178

Yan M, Liu X, Dang Q, Huang H, Yang F, Li Y. Intra-articular injection of human synovial membrane-derived mesenchymal stem cells in murine collagen-induced arthritis: assessment of immunomodulatory capacity in vivo. Stem cells international. 2017; 2017.

Chai NL, Zhang XB, Chen SW, Fan KX, Linghu EQ. Umbilical cord-derived mesenchymal stem cells alleviate liver fibrosis in rats. World journal of gastroenterology. 2016; 22(26):6036-6048. https://doi.org/10.3748/wjg.v22.i26.6036 PMid:27468195 PMCid:PMC4948270

Andia I, Maffulli N. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat Rev Rheumatol. 2013; 141:1-10. https://doi.org/10.1038/nrrheum.2013.141

Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS, Ra JC. Intraâ€articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proofâ€ofâ€concept clinical trial. Stem cells. 2014; 32(5):1254-66. https://doi.org/10.1002/stem.1634 PMid:24449146

Chung JY, Song M, Ha CW, Kim JA, Lee CH, Park YB. Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model. Stem cell research & therapy. 2014; 5(2):39. https://doi.org/10.1186/scrt427 PMid:24646697 PMCid:PMC4055114