Optimization of the Duration of the Administration of Mesenchymal Stem Cells Wharton’s Jelly to the Level of Matrix Metalloproteinase-1 and Transforming Growth Factor-β in Osteoarthritis Rat Model


  • Endrinaldi Endrinaldi Department of Biochemistry, Faculty of Medicine, Andalas University, Padang, Indonesia
  • Hirowati Ali Department of Biochemistry, Faculty of Medicine, Andalas University, Padang, Indonesia
  • Tofrizal Tofrizal Department of Anatomical Pathology, Faculty of Medicine, Andalas University, Padang, Indonesia
  • Asterina Asterina Department of Biochemistry, Faculty of Medicine, Andalas University, Padang, Indonesia
  • Elmatris Elmatris Department of Biochemistry, Faculty of Medicine, Andalas University, Padang, Indonesia
  • Sisca Dwi Yarni Biomedical Analyst, Department of Biotechnology, Faculty of Medicine, Andalas University, Padang, Indonesia




Osteoarthritis, Mesenchymal stem cell Wharton’s jelly, MMP-1, TGF-β1


BACKGROUND: Mesenchymal Stem Cell Wharton’s Jelly (MSC-WJ) is promising candidates for osteoarthritis (OA) therapy since they have chondrogenic potential and the ability to form the extracellular matrix.

AIM: This study aimed to determine the effect of the time giving MSC-WJ on bioactive markers of osteoarthritis.

METHODS: The osteoarthritis rat model was treated by intra-articular injection with MSC-WJ and α _MEM as a control. Four and 8 weeks later performed a histological analysis of cartilage and the determination of the levels of Matrix Metalloproteinase-1(MMP-1) and Transforming growth factor β1 (TGF-β1) in serum by ELISA.

RESULTS: The results showed that administration of MSC-WJ showed improvement in the histological picture of knee joints in experimental animals characterized by an increase in cartilage thickness on the joint surface. The administration of MSC-WJ showed a tendency to decrease MMP-1 serum levels of OA rats treated for 8 weeks, although statistically did not show a significant difference. Whereas, administration of MSC-WJ showed a decrease in serum levels of TGF-β1 OA rat treated for 8 weeks.

CONCLUSION: MSC-WJ can repair damaged knee OA cartilage tissue. The administration of MSC-WJ can reduce serum levels of TGF-β1 OA rats treated for 8 weeks.


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Martel-Pelletier J. Pathophysiology of osteoarthritis. Osteoarthritis Cartilage 2004;12 (Suppl A):S31-3. https://doi.org/10.1016/j.joca.2003.10.002 PMid:14698638 DOI: https://doi.org/10.1016/j.joca.2003.10.002

Goldring MB. Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep 2000a;2(6):459-65. https://doi.org/10.1007/s11926-000-0021-y PMid:11123098 DOI: https://doi.org/10.1007/s11926-000-0021-y

Felson DT. Osteoarthritis of the Knee. N Engl J Med. 2006;354(8):841-8. https://doi.org/10.1056/nejmcp051726 PMid:16495396 DOI: https://doi.org/10.1056/NEJMcp051726

Goldring MB. The role of the condrocyte in osteoarthritis. Arthritis Rheum. 2000b;43(9):1916-26. https://doi.org/10.1002/1529-0131(200009)43:9<1916:aid-ANR2>3.0.CO;2-I PMid:11014341 DOI: https://doi.org/10.1002/1529-0131(200009)43:9<1916::AID-ANR2>3.0.CO;2-I

Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther. 2009;11(3):224. https://doi.org/10.1186/ar2592 PMId:19519926 DOI: https://doi.org/10.1186/ar2592

Yan Z, Xiong J, Zhao C, Qin C, He C. Decreasing cartilage damage in a rat model of osteoarthritis by intraarticular injection of deoxycholic acid. Int J Clin Exp Med. 2015;8(6):9038-45. PMId:26309557

Fahmi H, Pelletier JP, Di Battista JA, Cheung ÜH, Fernandes JC, 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. Osteoarthritis Cartilage. 2002;10(2):100-8. https://doi.org/10.1053/joca.2001.0485 PMid:11869069 DOI: https://doi.org/10.1053/joca.2001.0485

Davidson EN, van der Kraan PM, van den Berg WB. TGF-β and osteoarthritis. Osteoarthritis Cartilage. 2007;15:597-604. https://doi.org/10.1016/j.joca.2007.02.005 PMid:17391995 DOI: https://doi.org/10.1016/j.joca.2007.02.005

Roberts AB, Sporn MB. Transforming growth factor β. Adv. Cancer Res. 1998;51:107-45. DOI: https://doi.org/10.1016/S0065-230X(08)60221-3

van der Kraan PM, van den Berg WB. Osteophytes: Relevance and biology. Osteoarthritis Cartilage. 2007;15(3):237-44. https://doi.org/10.1016/j.joca.2006.11.006 PMid:17204437 DOI: https://doi.org/10.1016/j.joca.2006.11.006

Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999284:143-7. https://doi.org/10.1126/science.284.5411.143 PMid:10102814 DOI: https://doi.org/10.1126/science.284.5411.143

Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, selfrenewaland differentiation. Arthritis Res Ther. 2007;9(1):204. https://doi.org/10.1186/ar2116 PMid:17316462 DOI: https://doi.org/10.1186/ar2116

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 DOI: https://doi.org/10.1371/journal.pone.0001886

Kalaszczynska I, Ferdyn K. Wharton’s jelly derived mesenchymal stem cells: Future of regenerative medicine? Recent findings and clinical significance. Biomed Res Int. 2015;2015:430847. https://doi.org/10.1155/2015/430847 PMid:25861624 DOI: https://doi.org/10.1155/2015/430847

Djouad F, Bouffi C, Ghannam S, Noël D, Jorgensen C. Mesenchymal stem cell: Innovative therapeutic tools for rheumatic diseases. Nat Rev Rheumatol. 2009;5(7):392-9. https://doi.org/10.1038/nrrheum.2009.104 PMid:19568253 DOI: https://doi.org/10.1038/nrrheum.2009.104

Koh YG, Choi YJ. Infrapatellar fat pad-derived mesenchymal stem cell therapy for knee osteoarthritis. Knee. 2012;19(6):902-7. https://doi.org/10.1016/j.knee.2012.04.001 PMid:22583627 DOI: https://doi.org/10.1016/j.knee.2012.04.001

Endrinaldi E, Darwin E, Zubir N, Revilla G. The effect of mesenchymal stem cell Wharton’s Jelly on Matrix Metalloproteinase-1 and Interleukin-4 levels in osteoarthritis rat model. Open Access Maced J Med Sci. 2019;7(4):529-35. https://doi.org/10.3889/oamjms.2019.152 PMid:30894907 DOI: https://doi.org/10.3889/oamjms.2019.152

Janusz MJ, Hookfin EB, Heitmeyer SA, Woessner JF, Freemont AJ, Hoyland JA, et al. Moderation of iodoacetateinduced experimental osteoarthritis in rats by matrix metalloproteinase inhibitors. Osteoarthritis Cartilage. 2001;9(8):751-60. https://doi.org/10.1053/joca.2001.0472 DOI: https://doi.org/10.1053/joca.2001.0472

Schuelert N, McDougall JJ. Grading of monosodium iodoacetate-induced osteoarthritis reveals a concentrationdependent sensitization of nociceptors in the knee joint of the rat. Neurosci Lett. 2009;465(2):184-8. https://doi.org/10.1016/j.neulet.2009.08.063 PMid:19716399 DOI: https://doi.org/10.1016/j.neulet.2009.08.063

Javanmard MZ, Asgari D, Karimipour M, Atabaki F, Farjah G, Niakani A. Mesenchymal stem cells inhibit proteoglycan degeneration in a rat model of osteoarthritis. Gene Cell Tisue. 2015;2(4):e31011. DOI: https://doi.org/10.17795/gct-31011

Guzman RE, Evan MG, Bove S, Morenko B, Kilgore K. Monoiodoacetate-induced histologic changes in subchondral boneand articular cartilage of rat femorotibial joints: An animal model of osteoarthritis. Toxicol Pathol. 2003;31(6):619-24. https://doi.org/10.1080/01926230390241800 PMid:14585729 DOI: https://doi.org/10.1080/01926230390241800

Deng MW, Wei SJ, Yew TL, Lee PH, Yang TY, Chu HY, et al. Cell therapy with G-CSF-mobilized stem cells in a rat osteoarthritis model. Cell Transplant. 2015;24(6):1085-96. https://doi.org/10.3727/096368914X680091 PMid:24667079 DOI: https://doi.org/10.3727/096368914X680091

Stracke JO, Fosang AJ, Last K, Mercuri FA, Pendas AM, Llano E, et al. Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP). FEBS Lett. 2000;478(1-2):52-6. https://doi.org/10.1016/s0014-5793(00)01819-6 PMid:10922468 DOI: https://doi.org/10.1016/S0014-5793(00)01819-6

De Groot J, Verzijl N, Marion JG, Wijk WV, Bank RA, Lafeber FP, et al. Age-related decrease in susceptibility of human articular cartilage to matrix metalloproteinase-mediated degradation. Arthritis Rheum. 2001;44(11):2562-71. https://doi.org/10.1002/1529-0131(200111)44:11<2562:aid-art437>3.0.co;2-1 PMid:11710713 DOI: 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 Res Ther. 2016;7(1):129. https://doi.org/10.1186/s13287-016-0393-1 PMid:27612636 DOI: https://doi.org/10.1186/s13287-016-0393-1

Tetlow LC, Adlam DJ, Woolley DE. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum. 2001;44(3):585-94. https://doi.org/10.1002/1529-0131(200103)44:3<585:AIDANR107>3.0.CO;2-C PMid:11263773 DOI: https://doi.org/10.1002/1529-0131(200103)44:3<585::AID-ANR107>3.0.CO;2-C

Ponte AL, Marais E, Gallay N, Langonne A, Delorme B, Herault O, et al. 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 DOI: https://doi.org/10.1634/stemcells.2007-0054

Chen MS, Lin CY, Chiu YH, Chen CP, Tsai PJ, Wang HS. IL-1β-induced matrix metalloprotease-1 promotes mesenchymal stem cell migration via PAR1 and G-protein-coupled signaling pathway. Stem Cells Int. 2018;2018:3524759. https://doi.org/10.1155/2018/3524759 PMid:30026761 DOI: https://doi.org/10.1155/2018/3524759

Saulnier N, Viguier E, Perrier-Groult E, Chenu C, Pillet E, Roger T, et al. 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 Cartilage. 2015;23(1):122-33. https://doi.org/10.1016/j.joca.2014.09.007 PMid:25219668 DOI: https://doi.org/10.1016/j.joca.2014.09.007

Widowati W, Afifah E, Mozef TJ, Sandra F, Rizal R, Amalia A, et al. Effects of insulin-like growth factorinduced Wharton jelly mesenchymal stem cells toward chondrogenesis in anosteoarthritis model. 2018. Iran J Basic Med Sci. 2018;21(7):745-52. https://doi.org/10.22038/IJBMS.2018.28205.6840 PMid:30140415

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

Lejmi E, Perriraz N, Clément S, Morel P, Baertschiger R, Christofilopoulos P, et al. Inflammatory chemokines MIP-1δ and MIP-3α are involved in the migration of multipotent mesenchymal stromal cells induced by hepatoma cells. Stem Cells Dev. 2015;24:1223-35. https://doi.org/10.1089/scd.2014.0176 PMid:25579056 DOI: https://doi.org/10.1089/scd.2014.0176

Ho IA, Chan KY, Ng WH, Guo CM, Hui KM, Cheang P, et al. Matrix metalloproteinase 1 is necessary for the migration of human bone marrow-derived mesenchymal stem cells toward human glioma. Stem Cells. 2009;27:1366-75. https://doi.org/10.1002/stem.50 PMid:19489099 DOI: https://doi.org/10.1002/stem.50

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 Tissue Biol. 2017;11(2):95-103. DOI: https://doi.org/10.1134/S1990519X17020092

Javelaud D, Mauviel A. Mammalian transforming growth factorbetas: Smad signaling and physio-pathological roles. Int J Biochem Cell Biol. 2004;36(7):1161-5. https://doi.org/10.1016/S1357-2725(03)00255-3 PMid:15109563 DOI: https://doi.org/10.1016/S1357-2725(03)00255-3

Xu L, Golshirazian I, Asbury BJ, Li Y. Induction of high temperature requirement A1, a serine protease, by TGFbeta1 in articular chondrocytes of mouse models of OA. Histol Histopathol. 2014;29(5):609-18. https://doi.org/10.14670/HH-29.10.609 PMid:24135912

Yang Y, Zhang D, Bai Y. Effect of TGF-β/Smads signaling in patients with osteoarthritis and osteoarthritis rat model. Int J Clin Exp Med. 2017;10(8):12172-8.

Rodrigues-Díez, R, Rayego-Mateos S, Orejudo M, Aroeira LS, Selgas R, Ortiz A, et al. TGF-beta blockade increases renal inflammation caused by the C-terminal module of the CCN2. Mediators Inflamm. 2015;2015:506041. DOI: https://doi.org/10.1155/2015/506041

Zhen G, Cao X. Targeting TGF-β signaling in subchondral bone and articular cartilage homeostasis. Trends Pharmacol Sci. 2014;35(5):227-36. https://doi.org/10.1016/j.tips.2014.03.005 PMid:24745631 DOI: https://doi.org/10.1016/j.tips.2014.03.005

van der Kraan PM. Differential role of transforming growth factor-beta in an osteoarthritic or a healthy joint. J Bone Metab. 2018;25(2):65-72. https://doi.org/10.11005/jbm.2018.25.2.65 PMid:29900155 DOI: https://doi.org/10.11005/jbm.2018.25.2.65

Zhen G, Wen C, Jia X, Li Y, Crane JL, Mears SC, et al. Inhibition of TGF-β signaling in subchondral bone mesenchymal stem cells attenuates osteoarthritis. Nat Med. 2013;19(6):704-12. https://doi.org/10.1038/nm.3143 PMid:23685840 DOI: https://doi.org/10.1038/nm.3143

Chen R, Mian M, Fu M, Zhao JY, Yang L, Li Y, et al. Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-beta1 signaling in a mouse model of osteoarthri-tis. Am J Pathol. 2015;185(11):2875-85. https://doi.org/10.1016/j.ajpath.2015.07.003 PMid:26355014 DOI: https://doi.org/10.1016/j.ajpath.2015.07.003

Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815-22. https://doi.org/10.1182/blood-2004-04-1559 PMid:15494428 DOI: https://doi.org/10.1182/blood-2004-04-1559

Abou Elkhier MT, Mohamed NN, Mourad MI. Therapeutic potential of intra-articular injection of bone marrow mesenchymal stem cells on tempromandibular joints’ induced osteoarthritis. An experimental study. J Dent Oral Biol. 2018;3(7):1150.




How to Cite

Endrinaldi E, Ali H, Tofrizal T, Asterina A, Elmatris E, Yarni SD. Optimization of the Duration of the Administration of Mesenchymal Stem Cells Wharton’s Jelly to the Level of Matrix Metalloproteinase-1 and Transforming Growth Factor-β in Osteoarthritis Rat Model. Open Access Maced J Med Sci [Internet]. 2022 Mar. 9 [cited 2023 Mar. 31];10(A):563-71. Available from: https://oamjms.eu/index.php/mjms/article/view/8838

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