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Correlation Between Synovial Fluid Levels of Matrix Metalloproteinase’s (MMP-1, MMP-3, and MMP-9) and TNF-α with the Severity of Osteoarthritis Knee in Rural Indian Population

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Abstract

Background

In India, 22% to 39% of the ageing population suffers from degenerative knee osteoarthritis (OA), making it the most prevalent joint disorder in the knee. MMP-1, MMP-3, and MMP-9 protein expression levels have all been associated with OA. The aim of the present study was to establish a relationship between synovial fluid levels of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9), and tumour necrosis factor-alpha (TNF-α) with different Kellgren–Lawrence Grading scale as per the severity of knee osteoarthritis (OA).

Methods

This hospital-based observational study included 87 individuals with knee osteoarthritis examined at the orthopaedics department outpatient clinic at the tertiary care teaching hospital in rural area of north India. In-person interviews were conducted to gather data, through a semi-structured, pretested interview schedule. To determine the degree and severity of OA, the levels of the enzymes matrix metalloproteinase MMP-1, MMP-3, and MMP-9 as well as tumour necrosis factor (TNF–α) were assessed in the synovial fluid of knee of each study participant.

Results

The levels of MMP-1, MMP-3, MMP-9, and TNF-α in synovial fluid were significantly correlated with the severity of osteoarthritis as determined by the Kellgren–Lawrence Grading Scale. Age, duration of symptoms and BMI showed a strong positive and significant correlation with biochemical markers (MMP-1, MMP-3, MMP-9, and TNF-α) in synovial fluid of Knee.

Conclusion

Level of biochemical markers (MMP-1, -3, -9, and TNF-α) in synovial fluid act as diagnostic markers and have a positive correlation with the severity of osteoarthritis knee, age, weight/BMI and duration of disease. However, no significant correlation was found between the level of aforementioned biochemical markers with sex, height, inflammation of the knee, morning stiffness, and age of onset of disease.

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References

  1. Sangha, O. (2000). Epidemiology of rheumatic diseases. Rheumatology (Oxford), 39(Suppl 2), 3–12. https://doi.org/10.1093/rheumatology/39.suppl_2.3. PMID: 11276800.

    Article  PubMed  Google Scholar 

  2. Kumar, H., Pal, C. P., Sharma, Y. K., Kumar, S., & Uppal, A. (2020). Epidemiology of knee osteoarthritis using Kellgren and Lawrence scale in Indian population. J Clin Orthop Trauma. https://doi.org/10.1016/j.jcot.2019.05.019

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zhang, Y., & Jordan, J. M. (2013). Epidemiology of osteoarthritis. Clinics in Geriatric Medicine. https://doi.org/10.1016/j.cger.2010.03.001

    Article  Google Scholar 

  4. Davis, M. A., Ettinger, W. H., Neuhaus, J. M., & Hauck, W. W. (1988). Sex differences in osteoarthritis of the knee: the role of obesity. American Journal of Epidemiology. https://doi.org/10.1093/oxfordjournals.aje.a114878

    Article  PubMed  Google Scholar 

  5. Symmons D, Mathers C, Pfleger B. Global Burden of Osteoarthritis in year 2000: Global burden of disease 2000 study. World health report. 2002;5 Version 2. Available from: https://www.who.int/healthinfo/statistics/bod_osteoarthritis.pdf.

  6. Blagojevic, M., Jinks, C., Jeffery, A., & Jordan, K. P. (2010). Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage, 18(1), 24–33. https://doi.org/10.1016/j.joca.2009.08.010. Epub 2009 Sep 2 PMID: 19751691.

    Article  CAS  PubMed  Google Scholar 

  7. Xu, L., Servais, J., Polur, I., Kim, D., Lee, P. L., Chung, K., & Li, Y. (2010). Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice. Arthritis and Rheumatism, 62(9), 2736–2744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Murphy, G., & Nagase, H. (2008). Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? Nat Clin PractRheumatol., 4(3), 128–135.

    Article  CAS  Google Scholar 

  9. Yoshihara, Y., Nakamura, H., Obata, K., et al. (2000). Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Annals of the Rheumatic Diseases, 59, 455–461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Burrage, P. S., Mix, K. S., & Brinckerhoff, C. E. (2006). Matrix metalloproteinases: role in arthritis. Frontiers in Bioscience, 1(11), 529–543. https://doi.org/10.2741/1817. PMID: 16146751.

    Article  Google Scholar 

  11. Hamerman, D. (1989). The biology of osteoarthritis. The New England J Med, 320, 1322–1330.

    Article  CAS  Google Scholar 

  12. Hulejová, H., Baresová, V., Klézl, Z., Polanská, M., Adam, M., & Senolt, L. (2007). Increased level of cytokines and matrix metalloproteinases in osteoarthritic subchondral bone. Cytokine, 38(3), 151–156. https://doi.org/10.1016/j.cyto.2007.06.001. Epub 2007 Aug 3 PMID: 17689092.

    Article  CAS  PubMed  Google Scholar 

  13. Little, C. B., Barai, A., Burkhardt, D., Smith, S. M., Fosang, A. J., Werb, Z., Shah, M., & Thompson, E. W. (2009). Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis and Rheumatism, 60(12), 3723–3733. https://doi.org/10.1002/art.25002.PMID:19950295;PMCID:PMC2832925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tío, L., Martel-Pelletier, J., Pelletier, J.-P., Bishop, P. N., & Roughley, P. (2014). AinaFarran, Pere Benito, Jordi Monfort, Characterization of opticin digestion by proteases involved in osteoarthritis development. Joint, Bone, Spine, 81, 2.

    Article  Google Scholar 

  15. Kardos, D., Marschall, B., Simon, M., Hornyák, I., Hinsenkamp, A., Kuten, O., Gyevnár, Z., Erdélyi, G., Bárdos, T., Paukovits, T. M., Magos, K., Béres, G., Szenthe, K., Bánáti, F., Szathmary, S., Nehrer, S., & Lacza, Z. (2019). Investigation of Cytokine Changes in Osteoarthritic Knee Joint Tissues in Response to Hyperacute Serum Treatment. Cells, 8(8), 824. https://doi.org/10.3390/cells8080824.PMID:31382623;PMCID:PMC6721638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Boffa, A., Merli, G., Andriolo, L., Lattermann, C., Salzmann, G. M., & Filardo, G. (2021). Synovial fluid biomarkers in knee osteoarthritis: a systematic review and quantitative evaluation using BIPEDs criteria. Cartilage. https://doi.org/10.1177/1947603520942941

    Article  PubMed  Google Scholar 

  17. Milaras, C., Lepetsos, P., Dafou, D., Potoupnis, M., & Tsiridis, E. (2021). Association of matrix metalloproteinase (MMP) gene polymorphisms with knee osteoarthritis: a review of the literature. Cureus. https://doi.org/10.7759/cureus.18607

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wassilew, G. I., Lehnigk, U., Duda, G. N., Taylor, W. R., Matziolis, G., & Dynybil, C. (2010). The expression of proinflammatory cytokines and matrix metalloproteinases in the synovial membranes of patients with osteoarthritis compared with traumatic knee disorders. Arthroscopy, 26(8), 1096–1104. https://doi.org/10.1016/j.arthro.2009.12.018. Epub 2010 Apr 8 PMID: 20678708.

    Article  PubMed  Google Scholar 

  19. Bourboulia, D., & Stetler-Stevenson, W. G. (2010). Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): positive and negative regulators in tumor cell adhesion. Seminars in Cancer Biology. https://doi.org/10.1016/j.semcancer.2010.05.002

    Article  PubMed  PubMed Central  Google Scholar 

  20. Murphy, G., Knauper, V., Atkinson, S., Butler, G., English, W., Hutton, M., et al. (2002). Matrix metalloproteinases in arthritic disease. Arthritis Research, 4(suppl 3), S39-49.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hemmann, S., Graf, J., Roderfeld, M., & Roeb, E. (2007). Expression of MMPs and TIMPs in liver fibrosis: a systematic review with special emphasis on anti-fibrotic strategies. Journal of Hepatology, 46(5), 955–975. https://doi.org/10.1016/j.jhep.2007.02.003. Epub 2007 Mar 5 PMID: 17383048.

    Article  CAS  PubMed  Google Scholar 

  22. Salgame, P. (2011). MMPs in tuberculosis: granuloma creators and tissue destroyers. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI57423

    Article  PubMed  PubMed Central  Google Scholar 

  23. Łukaszewicz-Zając, M., Mroczko, B., & Słowik, A. (2014). Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the tumors of central nervous system (CNS). Journal of Neural Transmission, 121(11), 1387–1397.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Cui, A., Li, H., et al. (2020). Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. The Lancet Research Paper. https://doi.org/10.1016/j.eclinm.2020.100587

    Article  Google Scholar 

  25. Silverwood, V., Blagojevic-Bucknall, M., Jinks, C., Jordan, J. L., Protheroe, J., & Jordan, K. P. (2015). Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage, 23(4), 507–515. https://doi.org/10.1016/j.joca.2014.11.019. Epub 2014 Nov 29 PMID: 25447976.

    Article  CAS  PubMed  Google Scholar 

  26. Oboirien M, Agbo SP, Ajiboye LO. Risk Factors in the Development of Knee Osteoarthritis in Sokoto, North West, Nigeria. International Journal of orthopaedics 2018; 5(2): 905–909 http://www.ghrnet.org/index.php/ijo/article/view/2258

  27. Ingale, D., Kulkarni, P., Electricwala, A., Moghe, A., Kamyab, S., Jagtap, S., Martson, A., Koks, S., & Harsulkar, A. (2021). Synovium-synovial fluid axis in osteoarthritis pathology: a key regulator of the cartilage degradation process. Genes, 12, 989. https://doi.org/10.3390/genes12070989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mahmoud, R. K., Elansary, A. K., Eleishi, H. H., Kamal, H. M., & Eisaeed, N. H. (2005). Matrix metalloproteinases MMP-3 and MMP-1 level in sera and synovial fluids in patients with rheumatoid arthritis and osteoarthritis. Italian Journal of Biochemistry, 54(34), 248–257.

    CAS  PubMed  Google Scholar 

  29. Tchetverikov, I., Lohmander, L., Verzijl, N., Huizinga, T., TeKoppele, J., Hanemaaijer, R., et al. (2005). MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Annals of the Rheumatic Diseases, 64(5), 694–698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Özler, K. (2018). Relationship of hematological and biochemical parameters with WOMAC index to severity of osteoarthritis: A retrospective study. Arch Clin Exp Med, 3(2), 84–87.

    Article  Google Scholar 

  31. Mandeville, D., Casazza, G., Alvarez, A., Sheremet, J., Waite, B., & Davis, B. (2013). Associations between Hormonal and Mechanical Factors of Knee Osteoarthritis in Women—A Preliminary Study. Open Journal of Rheumatology and Autoimmune Diseases, 3(2), 79–85. https://doi.org/10.4236/ojra.2013.32012

  32. Zeng, G. Q., Chen, A. B., Li, W., Song, J. H., & Gao, C. Y. (2015). High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis. Genetics and Molecular Research, 14(4), 14811–14822.

    Article  CAS  PubMed  Google Scholar 

  33. Jarecki, J., Małecka, M., et al. (2022). Concentration of Selected Metalloproteinases and Osteocalcin in the Serum and Synovial Fluid of Obese Women with Advanced Knee Osteoarthritis. International Journal of Environmental Research and Public Health. https://doi.org/10.3390/ijerph19063530

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedics, Uttar Pradesh University of Medical Sciences, Saifai, Etawah, India

    Sunil Kumar, Harish Kumar, Ankit Mittal, Prashant Pratap Singh, Vikas Yadav, Dinesh Kumar, Ishan Ahmad & Vyutpanna Mishra

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Kumar, S., Kumar, H., Mittal, A. et al. Correlation Between Synovial Fluid Levels of Matrix Metalloproteinase’s (MMP-1, MMP-3, and MMP-9) and TNF-α with the Severity of Osteoarthritis Knee in Rural Indian Population. JOIO 57, 1659–1666 (2023). https://doi.org/10.1007/s43465-023-00974-8

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