Serum Metalloproteinase-2 and Tissue İnhibitor Metalloproteinase-1 Levels As a Biomarker in Patients With Osteoarthritis Due To Brucella İnfection

Yıl 2022, Cilt: 13 Sayı: 3, 410 - 418, 20.12.2022

Mustafa Güzel , Orhan Akpınar , Veysel Atilla Ayyıldız , Mümtaz Cem Şirin

https://doi.org/10.22312/sdusbed.1138497

Öz

Objectives: It was aimed to investigate the usability of MMP-2 and TIMP-1 levels as biomarkers in the oosteoarticular complications of brucellosis.
Methods: The subjects were categorized into three groups as the healthy control group, brucella group, and brucella patients with osteoarticular involvement groups. Before medical treatment, serum samples from patients and control groups were stored at -80ºC until the day of study. MMP-2 and TIMP-1 serum levels were quantified by the ELISA method.
Results: Serum level of MMP-2 (mean ± SD) in healthy control group was 1.71 +/- 0.10 ng / mL. Brucella patient group and Osteoarticular complıcation group were 14.3 +/- 2.52 ng / ml 20.65 +/- 2.33 ng / ml respectively (p=0.001). The mean TIMP-1 level in the control group was 3578.96 +/- 67.2 ng / mL, while in the Brucella group, this rate was 998.27 +/- 66.7 ng / mL and in the bone involvement group, 1656. 17 +/- 17.3 ng / ml. The difference between the control group and the brucella patients and the complicated group was statistically significant (p= 0.001).
Conclusions: We think that the significant change in serum levels of MMP-2 and TIMP-1 when evaluated together with the radiological method, can be used as a biochemical indicator of the development of osteoarticular complications.

Anahtar Kelimeler

Brucellozis, MMP-2, TIMP-1, biomarker, osteoarticuler complication

Brucella Enfeksiyonuna Bağlı Osteoartritli Hastalarda Biyobelirteç Olarak Serum Metalloproteinaz-2 ve Doku İnhibitörü Metalloproteinaz-1 Seviyeleri

Öz

Amaç: Brusellozun oosteoartiküler komplikasyonlarında MMP-2 ve TIMP-1 düzeylerinin biyobelirteç olarak kullanılabilirliğinin araştırılması amaçlandı.

Metot: Olgular sağlıklı kontrol grubu, brusella grubu ve osteoartiküler tutulumu olan brusella hastaları olarak üç gruba ayrıldı. Medikal tedavi öncesi hasta ve kontrol gruplarından alınan serum örnekleri çalışma gününe kadar -80ºC'de saklandı. MMP-2 ve TIMP-1 serum seviyeleri, ELISA yöntemiyle ölçüldü.

Bulgular: Sağlıklı kontrol grubunda MMP-2 (ortalama ± SD) serum düzeyi 1,71 +/- 0,10 ng / mL idi. Brusella hasta grubu ve Osteoartiküler komplikasyon grubunda sırasıyla 14,3 +/- 2,52 ng / ml 20,65 +/- 2,33 ng / ml idi (p=0,001). Kontrol grubunda ortalama TIMP-1 düzeyi 3578,96 +/- 67,2 ng/ml iken, Brucella grubunda bu oran 998,27 +/- 66,7 ng/ml, kemik tutulumu grubunda 1656, 17 +/- 17,3 ng / ml idi . Kontrol grubu ile brusella hastaları ve komplike grup arasındaki fark istatistiksel olarak anlamlıydı (p= 0,001).

Sonuç: Radyolojik yöntemle birlikte değerlendirildiğinde, MMP-2 ve TIMP-1 serum seviyelerindeki önemli değişiklik, brusellozun osteoartiküler komplikasyonlarının gelişiminin biyokimyasal bir göstergesi olarak kullanılabileceğini düşünüyoruz.

Anahtar Kelimeler

Brusellozis, MMP-2, TIMP-1, Biyobelirteç, osteoartiküler komplikasyon

Kaynakça

• [1] Young, E.J. 2010. Brucella Species. Ss 2921-25. Mandell GL, Douglas RG, Bennett JE.,7th ed.2010. Principles and Practice of Infectious Diseases. Churchill Livingstone,Philadelphia,USA, 4028s
• [2] Akpinar, O. 2016. Historical perspective of brucellosis: a microbiological and epidemiological overview. Le Infezioni in Medicina, 24(1),77-86.
• [3] Corbel, M. J. 2006. Brucellosis in humans and animals. World Health Organization. CDS/EPR/2006.7, 89s.
• [4] Franco, M. P., Mulder, M., Gilman, R. H.,Smits, H. L. 2007. Human brucellosis. The Lancet infectious diseases, 7(12), 775-786.
• [5] Akpınar, O., Kılıç, H. (2012). Bruselloz: 382 olgunun geriye dönük irdelenmesi. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi, 3(3), 108-113.
• [6] Ibero, I., Vela, P., & Pascual, E. (1997). Arthritis of shoulder and spinal cord compression due to Brucella disc infection. British journal of rheumatology, 36(3), 377-381.
• [7] Duman, A., & Akpınar, O. (2016). Brucellar spondylodiscitis in chronic low back pain patients. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi, 7(3), 63-65.
• [8] Burrage, P. S., Mix, K. S., Brinckerhoff, C. E. 2006) Matrix metalloproteinases: role in arthritis. Frontiers in Bioscience-Landmark, 11(1), 529-543.
• [9]Nagase H, Woessner JFJr. 1999.Matrix metalloproteinases. J Biol Chem ,274,21491-4.
• [10] Lambert, E., Dassé, E., Haye, B., Petitfrère, E. 2004. TIMPs as multifacial proteins. Critical reviews in oncology/hematology, 49(3), 187-198.
• [11] Behera, A. K., Hildebrand, E., Scagliotti, J., Steere, A. C., Hu, L. T. 2005. Induction of host matrix metalloproteinases by Borrelia burgdorferi differs in human and murine Lyme arthritis. Infection and immunity, 73(1), 126-134.
• [12] Delpino, M. V., Fossati, C. A., Baldi, P. C. 2009. Proinflammatory response of human osteoblastic cell lines and osteoblast-monocyte interaction upon infection with Brucella spp. Infection and immunity, 77(3), 984-995.
• [13 ]Scian, R., Barrionuevo, P., Fossati, C. A., Giambartolomei, G. H.,Delpino, M. V. 2012. Brucella abortus invasion of osteoblasts inhibits bone formation. Infection and immunity, 80(7), 2333-2345.
• [14] Kohno, Y., Tanimoto, A., Cirathaworn, C., Shimajiri, S., Tawara, A., Sasaguri, Y. 2004. GM‐CSF activates RhoA, integrin and MMP expression in human monocytic cells. Pathology international, 54(9), 693-702.
• [15] Krubasik, D., Eisenach, P. A., Kunz‐Schughart, L. A., Murphy, G., English, W. R. 2008. Granulocyte‐macrophage colony stimulating factor induces endothelial capillary formation through induction of membrane‐type 1 matrix metalloproteinase expression in vitro. International journal of cancer, 122(6), 1261-1272.
• [16] Scian, R., Barrionuevo, P., Giambartolomei, G. H., Fossati, C. A., Baldi, P. C., & Delpino, M. V. (2011). Granulocyte-macrophage colony-stimulating factor-and tumor necrosis factor alpha-mediated matrix metalloproteinase production by human osteoblasts and monocytes after infection with Brucella abortus. Infection and immunity, 79(1), 192-202.
• [17] Saklatvala J, Nagase H, Salvesen G, Brew K. 2003. Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors. Biochem Soc Symp, 70:201-12.
• [18] Šiširak, M., & Hukić, M. (2015). Osteoarticular complications of brucellosis: The diagnostic value and importance of detection matrix metalloproteinases. Acta medica academica, 44(1), 1.
• [19]Cawston, T. 1993. Blocking cartilage destruction with metalloproteinase inhibitors: a valid therapeutic target?. Annals of the rheumatic diseases, 52(11), 769.
• [20]Galis, Z. S., & Khatri, J. J. (2002). Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circulation research, 90(3), 251-262.
• [21]Jacob, M. P., Badier-Commander, C., Fontaine, V., Benazzoug, Y., Feldman, L., Michel, J. B. 2001. Extracellular matrix remodeling in the vascular wall. Pathologie Biologie, 49(4), 326-332.
• [22]Brinckerhoff, C. E., & Matrisian, L. M. 2002. Matrix metalloproteinases: a tail of a frog that became a prince. Nature reviews Molecular cell biology, 3(3), 207-214.
• [23]Kevorkian, L., Young, D. A., Darrah, C., Donell, S. T., Shepstone, L., Porter, S., Clark, I. M. 2004. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, 50(1), 131-141.
• [24]Malemud, C. J., Islam, N., Haqqi, T. M. 2003. Pathophysiological mechanisms in osteoarthritis lead to novel therapeutic strategies. Cells Tissues Organs, 174(1-2), 34-48.
• [25] Murphy, G., Lee, M. H. 2005. What are the roles of metalloproteinases in cartilage and bone damage?. Annals of the rheumatic diseases, 64(suppl 4), iv44-iv47.