Skip to main content
The Egyptian Journal of Internal Medicine
Download PDF
  • Original article
  • Open access
  • Published:

Serum and synovial matrix metalloproteinases 1 and 3 in patients with early rheumatoid arthritis: potentially prospective biomarkers of ultrasonographic joint damage and disease activity

The Egyptian Journal of Internal Medicine volume 31, pages 965–971 (2019)Cite this article

Abstract

Background

Matrix metalloproteinase-1 (MMP-1) and MMP-3 play important roles in the pathogenesis of rheumatoid arthritis (RA) and have been suggested as markers of disease activity and joint damage.

Objective The aim was to analyze the clinical significance of MMP-1 and MMP-3 in relation to markers of disease activity and degree of joint destruction in patients with early RA at presentation and after 6 months.

Patients and methods

Baseline levels of serum MMP-1 and MMP-3 were assessed in 50 patients with early RA (symptoms <1 year), 20 patients with osteoarthritis (OA), and 20 age-matched and sex-matched healthy controls. Serum MPP-1 and MPP-3 were correlated with disease activity markers [erythrocyte sedimentation rate (ESR), C-reactive protein, disease activity score 28–ESR] and radiographic joint damage using simple erosion narrowing score and musculoskeletal ultrasound of wrist and hand joints. Baseline synovial fluid MMP-1 and MMP-3 levels were evaluated for 20 patients indicated for arthrocentesis.

Results

Baseline serum MMP-1 and MMP-3 were significantly higher in RA group versus OA group and healthy controls (P<0.001). Synovial MMP-1 and MMP-3 levels were significantly higher in RA versus OA group. Serum MMP-1 and MMP-3 levels significantly correlated with rheumatoid factor titers, anticyclic citrullinated peptide, disease activity score 28-ESR score, joint erosions, and Outcome Measures in Rheumatology score of synovitis and Doppler signals. Serum MMP-1 did not correlate with C-reactive protein, but significantly correlated with the number of erosions at presentation and on follow-up. The number of patients with erosions and the number of erosions per patient increased after 6 months and correlated with serum MMP-1 and MMP-3. The best cutoff values of serum MMP-1 and MMP-3 to discriminate between RA and healthy controls were greater than 20 and greater than 50ng/ml, respectively.

Conclusion

Elevated serum levels of MMP-1 and MMP-3 can be used as an indicator of disease activity in patients with early RA and can reflect the degree of joint damage and correlate with the number of new joint erosions.

References

  1. Murakami K, Mimori T. Diagnosis and treatment of rheumatoid arthritis: toward the best practice. The Pathophysiology in Rheumatoid Arthritis. Clin Calcium 2018; 28:595–600.

    CAS  PubMed  Google Scholar 

  2. Emery P, Salmon M. Early rheumatoid arthritis: time to aim for remission? Ann Rheum Dis 1995; 54:944–947.

    Article  CAS  Google Scholar 

  3. Finckh A. Early inflammatory arthritis versus rheumatoid arthritis. Curr Opin Rheumatol 2009; 21:118–123.

    Article  Google Scholar 

  4. Ma JD, Zhou JJ, Zheng DH, Chen LF, Mo YQ, Wei XN, et al. Serum matrix metalloproteinase-3 as a noninvasive biomarker of histological synovitis for diagnosis of rheumatoid arthritis. Mediators Inflamm 2014; 2014:179284.

    Article  Google Scholar 

  5. Mulherin D, FitzGerald O, Bresnihan B. Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ. Br J Rheumatol 1996; 35:1263–1268.

    Article  CAS  Google Scholar 

  6. Tchetverikov I, Lohmander LS, Verzijl N, Huizinga T, TeKoppele J, Hanemaaijer R, et al. MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann Rheum Dis 2005; 64:694–698.

    Article  CAS  Google Scholar 

  7. Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci 2006; 11:529–543.

    Article  CAS  Google Scholar 

  8. Ribbens C, Martin Y, Porras M, Kaiser MJ, Jaspar JM, Damas P, et al. Increased matrix metalloproteinase-3 serum levels in rheumatic diseases: relationship with synovitis and steroid treatment. Ann Rheum Dis 2002; 61:161–166.

    Article  CAS  Google Scholar 

  9. Gheita TA, Abdel Rehim DM, Kenawy SA, Gheita HA. Clinical significance of matrix metalloproteinase-3 in systemic lupus erythematosus patients: a potential biomarker for disease activity and damage. Acta Reumatol Port 2015; 40:145–149.

    CAS  PubMed  Google Scholar 

  10. Dickinson SC, Vankemmelbeke MN, Buttle DJ, Rosenberg K, Heinegård D, Hollander AP. Cleavage of cartilage oligomeric matrix protein (Thrombospondin-5) by matrix metalloproteinases and a disintegrin and metalloproteinase with thrombospondin motifs. Matrix Biol 2003; 22:267–278.

    Article  CAS  Google Scholar 

  11. El Defrawy AO, Gheita TA, Raslan HM, El Ansary MM, El Awar AH. Serum and synovial cartilage oligomeric matrix protein levels in early and established rheumatoid arthritis. Z Rheumatol 2016; 75:917–923.

    Article  Google Scholar 

  12. Gheita TA, Hussein H. Cartilage Oligomeric Matrix Protein (COMP) in systemic sclerosis (SSc): role in disease severity and subclinical rheumatoid arthritis overlap. Joint Bone Spine 2012; 79:51–56.

    Article  CAS  Google Scholar 

  13. Cunnane G, FitzGerald O, Beeton C, Cawston TE, Bresnihan B. Early joint erosions and serum levels of matrix metalloproteinase 1, matrix metalloproteinase 3, and tissue inhibitor of metalloproteinases 1 in rheumatoid arthritis. Arthritis Rheum 2001; 44:2263–2274.

    Article  CAS  Google Scholar 

  14. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO III, et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Ann Rheum Dis 2010; 62:2569–2581.

    Google Scholar 

  15. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 1986; 29:1039–1049.

    CAS  PubMed  Google Scholar 

  16. Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL, et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995; 38:44–48.

    CAS  Google Scholar 

  17. Van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 2000; 27:261–263.

    PubMed  Google Scholar 

  18. Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Ann Rheum Dis 1957; 16:494–502.

    Article  CAS  Google Scholar 

  19. Wakefield RJ, Balint PV, Szkudlarek M, Filippucci E, Backhaus M, D’Agostino MA, et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol 2005; 32:2485–2487.

    PubMed  Google Scholar 

  20. Jain A, Nanchahal J, Troeberg L, Green P, Brennan F. Production of cytokines, vascular endothelial growth factor, matrix metalloproteinases, and tissue inhibitor of metalloproteinases 1 by teno-synovium demonstrates its potential for tendon destruction in rheumatoid arthritis. Arthritis Rheum 2001; 44:1754.

    Article  CAS  Google Scholar 

  21. Zhou L, Song J, Chen L, Xu HJ. The application of matrix metalloproteinase-3 and 7 joints ultrasonic score in assessment of disease activity in patients with rheumatoid arthritis. Zhong huanei kezazhi 2017; 55:531–534.

    Google Scholar 

  22. Al-Sebaie MA, AL-Yasaky AZ, Assaf NY, Mohammad M. Serum and synovial fluid levels of MMP-3 and TIMP-1 in rheumatoid arthritis and osteoarthritis. Egypt Rheumatol Rehab 2003; 30:841–860.

    Google Scholar 

  23. Mahmoud RK, El-Ansary AK, El-Eishi HH, Kamal HM, El-Saeed NH. Matrix metalloproteinases MMP-3 and MMP-1 levels in sera and synovial fluids in patients with rheumatoid arthritis and osteoarthritis. Ital J Biochem 2005; 54:248–257.

    CAS  PubMed  Google Scholar 

  24. Ally MMTM, Hodkinson B, Meyer PWA, Musenge E, Tikly M, Anderson R. Serum matrix metalloproteinase-3 in comparison with acute phase proteins as a marker of disease activity and radiographic damage in early rheumatoid arthritis. Mediators Inflamm 2013; 2013:183653.

    Article  Google Scholar 

  25. Ali OSM, Khalifa AIM, El-Shaer SSM, Ghouraba AF. Study of the diagnostic value of anti-MCV and MMP3 biomarkers in serum and synovial fluid of rheumatoid arthritis patients, Int J Pharm Appl 2015; 16: 19–20.

    Google Scholar 

  26. Kobayashi A, Naito S, Enomoto H, Shiomoi T, Kimura T, Obata K, et al. Serum levels of matrix metalloproteinase 3 (stromelysin 1) for monitoring synovitis in rheumatoid arthritis. Arch Pathol Lab Med 2007; 131:563–570.

    Article  CAS  Google Scholar 

  27. Fawzy RM, Abdel Hamid YA, Albehesy MM, Aboelmagd RF. Serum and synovial matrix metalloproteinase-3 as markers of disease activity in early rheumatoid arthritis. Egypt Rheumatol Rehabil 2016; 43:178–183.

    Article  Google Scholar 

  28. Posthumus MD, Limburg PC, Westra J, van Leeuwen MA, van Rijswijk MH. Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression. J Rheumatol 2000; 27:2761–2768.

    CAS  PubMed  Google Scholar 

  29. Ateş A, Türkçapar N, Olmez U, Tiryaki O, Düzgün N, Uğuz E, et al. Serum pro-matrix metalloproteinase-3 as an indicator of disease activity and severity in rheumatoid arthritis: comparison with traditional markers. Rheumatol Int 2007; 27:715–722.

    Article  Google Scholar 

  30. Fadda S, Abolkheir E, Afifi R, Gamal M. Serum matrix metalloproteinase-3 in rheumatoid arthritis patients: Correlation with disease activity and joint destruction. Egypt Rheumatol 2016; 38:153–159.

    Article  Google Scholar 

  31. Li L, Cai B, Liao J, Yang B, Huang Z, Wang L. Clinical value of serum matrix metalloproteinase-3 in evaluating joint destruction and therapeutic effect in rheumatoid arthritis patients. Xi Bao Yu Fen ZiMian Yi XueZa kjjZhi 2013; 29:966–969.

    CAS  Google Scholar 

  32. Uemura Y, Hayashi H, Takahashi T, Saitho T, Umeda R, Ichise Y, et al. MMP-3 as a biomarker of disease activity of rheumatoid arthritis. Rinsho Byori 2015; 63:1357–1364.

    CAS  PubMed  Google Scholar 

  33. Ma JD, Wang JW, Xu YH, Yang KM, Chen LF, Lin JZ, Dai L. Serum MMP-3 more than 155 ng/ml at baseline predicts one-year radiographic progression in patients with rheumatoid Arthritis [abstract no 1498]. Arthritis Rheumatol 2018; 70:1650.

    Google Scholar 

  34. Goral WM, Ogasawara M, Matsuki Y, Yamada Y, Murayama G, Sugisaki N, et al. Weighting with the Lansbury articular index improves the correlation of ultrasound score with serum matrix metalloproteinase-3 level in rheumatoid arthritis patients. Mod Rheumatol 2014; 24:915–919.

    Article  Google Scholar 

  35. Galil SMA, El-Shafey AM, Hagrass HA, Fawzy F, Sammak AE. Baseline serum level of matrix metalloproteinase-3 as a biomarker of progressive joint damage in rheumatoid arthritis patients. Int J Rheum Dis 2014; 19:377–384.

    Article  Google Scholar 

  36. Shinozaki M, Inoue E, Nakajima A, Hara M, Tomatsu T, Kamatani N, et al. Elevation of serum matrix metalloproteinase-3 as a predictive marker for the long-term disability of rheumatoid arthritis patients in a prospective observational cohort IORRA. Mod Rheumatol 2007; 17:403–408.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine and Rheumatology, Faculty of Medicine, Ain Shams University, Cairo, 11865, Egypt

    Maryam A. Abdelrahman MSc& MD of Internal Medicine & Naglaa Afifi

  2. Department of Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Hossam M. Sakr

  3. Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Menat A. A. Shaaban

Authors
  1. Maryam A. Abdelrahman MSc& MD of Internal Medicine
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hossam M. Sakr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Menat A. A. Shaaban
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naglaa Afifi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maryam A. Abdelrahman MSc& MD of Internal Medicine.

Additional information

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdelrahman, M.A., Sakr, H.M., Shaaban, M.A.A. et al. Serum and synovial matrix metalloproteinases 1 and 3 in patients with early rheumatoid arthritis: potentially prospective biomarkers of ultrasonographic joint damage and disease activity. Egypt J Intern Med 31, 965–971 (2019). https://doi.org/10.4103/ejim.ejim_163_19

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/ejim.ejim_163_19

Keywords