Sinovyal sıvıdaki adamts5 proteaz enzimi ile gonartrozun klinik ve radyolojik bulguları arasındaki ilişki

Öz

Amaç: Bu çalışma, diz eklemi rahatsızlıkları olan bireylerin sinovyal sıvısındaki ADAMTS5 enzimi seviyeleri ile fonksiyonel durum, klinik ve radyolojik bulgular arasındaki ilişkiyi araştırmıştır. Gereç ve Yöntem: Bu çalışma, Ocak 2016'dan Aralık 2022'ye kadar Ortopedi ve Travmatoloji Anabilim Dalı'na diz ağrısı nedeniyle başvuran 18-75 yaş arası 240 hastayı içermektedir. Hastalar, Amerikan Romatoloji Koleji kriterlerine göre primer diz osteoartriti tanısı aldı ve Kellgren-Lawrence ölçeği kullanılarak değerlendirildi. ELISA yöntemi, araştırmaya katılan bireylerin diz eklemlerinden elde edilen sinovyal sıvı örneklerinde ADAMTS5 seviyelerini değerlendirmek için kullanıldı. Bulgular: Sinovyal sıvılardaki ADAMTS5 seviyeleri ile hastalığın evresi, hastaların yaşı ve WOMAC puanları arasında istatistiksel olarak anlamlı bir ilişki tespit edildi. Ancak, sinovyal sıvılardaki ADAMTS5 seviyeleri ile hastaların cinsiyeti ve hastalıklı tarafları arasında istatistiksel olarak anlamlı bir korelasyon bulunmamıştır. Bu bulgular, bireyler yaşlandıkça sinovyal sıvılardaki ADAMTS5 seviyelerinin düştüğünü ve bunun Osteoartrit'in başlangıcı ve ilerlemesine yol açtığını göstermektedir. Tartışma: Benzer çalışmalar, osteoartrit ile ADAMTS, ADAMTS proteaz ailesinin bir üyesi arasında güçlü bir bağlantı buldu. Farelerde, ADAMTS5'in ana aggrekanaz olduğu bulunmuştur. Syndecan-4'ün inhibe edilmesi, osteoartritte kıkırdak dejenerasyonunun tedavisini kolaylaştırabilir. ADAMTS5 miktarı ile osteoartrit aşaması arasında istatistiksel olarak anlamlı bir negatif ilişki bulundu. Yaş ile osteoartritin başlangıcıyla bağlantılı olan sinovyal sıvıdaki ADAMTS5 miktarı arasında da negatif bir ilişki vardı. Sonuç: Gelecekte, Osteoartrit ve Romatoid Artrit gibi hastalıklarda kıkırdak matrisinin bozulmasından sorumlu ADAMTS enzimleri için yeni ilaçların keşfedilmesi veya oluşturulması, daha fazla sayıda hastayı içeren denemelerle mümkün olabilir.

Anahtar Kelimeler

• osteoartrit
• WOMAC skoru
• ADAMTS
• agrekanaz

Proje Numarası

Date and number: 13.04.2016/4

The relationship between the clinical and the radiological findings of gonarthrosis with adamts5 protease enzyme in synovial liquid

Öz

Aim: This study investigated the relationship between functional status, clinical and radiological findings, and the levels of the ADAMTS5 enzyme in the synovial fluid of individuals with knee joint conditions. Material And Method: This study included 240 patients aged 18-75 who sought treatment for knee pain at the Orthopedics and Traumatology Department from January 2016 to December 2022. Patients were diagnosed with primary knee osteoarthritis based on the American Rheumatology College criteria and were assessed using the Kellgren-Lawrence scale. The ELISA method was used to evaluate the levels of ADAMTS5 in synovial fluid samples obtained from the knee joints of the individuals involved in the investigation. Results: A statistically significant association was established between the levels of ADAMTS5 in synovial fluids and the stage of disease, age of patients, and WOMAC scores. However, there was no statistically significant correlation between ADAMTS5 levels in synovial fluids and the gender and ill sides of patients. These findings indicate that as individuals age, there is a decline in ADAMTS5 levels in synovial fluids, leading to the onset and progression of Osteoarthritis. Discussion: Similar studies found a strong connection between osteoarthritis and ADAMTS, a member of the ADAMTS protease family. In mice, ADAMTS5 was found to be the main aggrecanase. Inhibiting syndecan-4 may facilitate the treatment of cartilage degeneration in osteoarthritis. A statistically significant negative relationship was found between the amount of ADAMTS5 and the stage of osteoarthritis. There was also a negative relationship between age and the amount of ADAMTS5 in synovial fluid, which is linked to the start of osteoarthritis. Conclusion: In the future, it may be feasible to uncover or create novel medications for ADAMTS enzymes, responsible for the degradation of cartilage matrix in illnesses like Osteoarthritis and Rheumatoid Arthritis, through trials involving a larger number of patients.

Anahtar Kelimeler

• osteoarthritis
• WOMAC score
• ADAMTS
• aggrecanase

Destekleyen Kurum

The present work did not receive any external support.

Proje Numarası

Date and number: 13.04.2016/4

Etik Beyan

The study was conducted in accordance with the principles outlined in the Declaration of Helsinki and received approval from the local ethics body, specifically the Clinical Research Ethics body of Turgut Özal University Faculty of Medicine. Date and number: April 13, 2016.

Teşekkür

Thank you for considering our work.

Kaynakça

1. 1. Jeschke A, Bonitz M, Simon M, Peters S, Baum W, Schett G, et al. Deficiency of Thrombospondin-4 in Mice Does Not Affect Skeletal Growth or Bone Mass Acquisition, but Causes a Transient Reduction of Articular Cartilage Thickness. PLoS One. 2015 Dec 2;10(12):e0144272. doi: 10.1371/journal.pone.0144272. PMID: 26629997; PMCID: PMC4667928.
2. 2. Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010 Aug;26(3):355-69. doi: 10.1016/j. cger.2010.03.001. Erratum in: Clin Geriatr Med. 2013 May;29(2):ix. PMID: 20699159; PMCID: PMC2920533.
3. 3. Szponder T, Latalski M, Danielewicz A, Krać K, Kozera A, Drzewiecka B, et al. Osteoarthritis: Pathogenesis, Animal Models, and New Regenerative Therapies. J Clin Med. 2022 Dec 20;12(1):5. doi: 10.3390/jcm12010005. PMID: 36614806; PMCID: PMC9821671.
4. 4. Li T, Peng J, Li Q, Shu Y, Zhu P, Hao L. The Mechanism and Role of ADAMTS Protein Family in Osteoarthritis. Biomolecules. 2022 Jul 8;12(7):959. doi: 10.3390/biom12070959. PMID: 35883515; PMCID: PMC9313267.
5. 5. Wang LW, Nandadasa S, Annis DS, Dubail J, Mosher DF, Willard BB, et al. A disintegrin-like and metalloproteinase domain with thrombospondin type 1 motif 9 (ADAMTS9) regulates fibronectin fibrillogenesis and turnover. J Biol Chem. 2019 Jun 21;294(25):9924-9936. doi: 10.1074/jbc.RA118.006479. Epub 2019 May 13. PMID: 31085586; PMCID: PMC6597835.
6. 6. Çiftçi, S. (2015). Ailevi Akdeniz Ateşi Hastalarında Serum Amiloid A, YKL-40 ve Pentraxin Düzeylerinin İncelenmesi (Tıpta Uzmanlık Tezi). Turgut Özal Üniversitesi, Basılmamış Tıpta Uzman- lık Tezi.
7. 7. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Oste- oarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012 Jun;64(6):1697-707. doi: 10.1002/art.34453. Epub 2012 Mar 5. PMID: 22392533; PMCID: PMC3366018.
8. 8. Dennisson E, Cooper C. Osteoarthritis: Epidemiology and classification, in Rheumatology, Mosby, 2003

9. 9. Felson DT, Radinb EL. What causes knee osteoarthritis: are different compartments susceptible to different risk factors? J Rheumatol 1994; 21:181-183
10. 10. Henry J, Mankin D. Pathogenesis of Osteoarthritis. Kel- ley.s Textbook of Rheumatology, sixth edition, volume II, Saunders Company, 2001
11. 11. Pai YC, Rymer WZ, Chang RW, Sharma L. Effect of age and osteoarthritis on knee proprioception. Arthritis Rheum 1997; 40(12):2260-65
12. 12. Hu Q, Ecker M. Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. Int J Mol Sci. 2021;22(4):1742. Published 2021 Feb 9. doi:10.3390/ijms22041742
13. 13. Yamamoto K, Wilkinson D, Bou-Gharios G. Targeting Dys- regulation of Metalloproteinase Activity in Osteoarthritis. Calcif Tis- sue Int. 2021;109(3):277-290. doi:10.1007/s00223-020-00739-7
14. 14. Zeng GQ, Chen AB, Li W, Song JH, Gao CY. High MMP1, MMP-2, and MMP-9 protein levels in osteoarthritis. Genet Mol Res. 2015;14(4):14811-14822. Published 2015 Nov 23. doi:10.4238/2015.November.18.46
15. 15. Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation. Arthritis Res Ther 2003;5(2):94-103. 106
16. 16. Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 2005;434(7033):644-8.
17. 17. Echtermeyer F, Bertrand J, Dreier R, Meinecke I, Neugebauer K, Fuerst M, et al. Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis. Nature medicine. 2009;15(9):1072-6. Epub 2009/08/18.
18. 18. Bau B, Gebhard PM, Haag J, Knorr T, Bartnik E, Aigner T. Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro. Arthritis and rheumatism. 2002;46(10):2648-57. Epub 2002/10/18.
19. 19. Kevorkian L, Young DA, Darrah C, Donell ST, Shepstone L, Porter S, et al. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis and rheumatism. 2004;50(1):131- 41. Epub 2004/01/20.
20. 20. Zhang E, Yan X, Zhang M, et al. Aggrecanases in the human synovial fluid at different stages of osteoarthritis. Clin Rheumatol. 2013;32(6):797-803. doi:10.1007/s10067-013-2171-