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Diz Osteoartrit Hastalarının Periferik Kan ve Kıkırdak Doku Örneklerinde Proinflamatuvar Sitokinlerin Etkilerinin Araştırılması

Year 2020, Volume: 6 Issue: 3, 373 - 381, 01.01.2020

Abstract

Amaç: Osteoartrit OA ağrı ve fonksiyon kısıtlılığıyla sonuçlanan dejeneratif bir eklem hastalığıdır. Metabolizmada düzenleyici moleküller olmaları ve OA patofizyolojisindeki rolleri nedeniyle sitokinler; tanı ve tedavi için araştırılan önemli faktörlerdendir. Bu çalışmanın amacı; IL-1β, IL-6, IL-17, IL-18 ve TNF-α proinflamatuvar sitokinlerinin OA ile ilişkisini göstermek ve kıkırdak dokusunda harabiyete neden olan bozulmuş katabolik aktivitelerini saptamaktır. Ayrıca bu moleküllerin kan ve kıkırdak dokularında kıyaslanarak tanı ve tedavi süreçleri için olası biyomarker adaylarının belirlenmesi amaçlanmıştır.Gereç ve Yöntemler: Hasta ve kontrol grubu olmak üzere ikiye ayrılan toplam 30 olgudan alınan periferik kan ve kıkırdak doku örneklerinde ilgili sitokinlerin protein düzeylerinin belirlenmesinde Western blot, gen ekspresyon seviyelerinin belirlenmesinde ise kantitatif gerçek zamanlı polimeraz zincir reaksiyonu yöntemleri uygulanmıştır. Ayrıca olguların C-reaktif protein CRP düzeyleri ve Kellgren-Lawrence K-L skorlamaları da sorgulanmıştır.Bulgular: Protein düzeyleri için dokuda IL-6, kanda ise IL-1β ve IL-17 istatistiksel olarak anlamlı bulunmuştur sırasıyla p

References

  • Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr AJ. Osteoarthritis. Lancet 2015; 386(9991):376-87.
  • Mobasheri A, Batt M. An update on the pathophysio- logy of osteoarthritis. Ann Phys Rehabil Med 2016; 59(5- 6):333-9.
  • Hosnijeh FS, Runhaar J, van Meurs JB, Bierma-Zeins- tra SM. Biomarkers for osteoarthritis: Can they be used for risk assessment? A systematic review. Maturitas 2015; 82(1):36-49.
  • Ishijima M, Kaneko H, Kaneko K. The evolving role of biomarkers for osteoarthritis. Ther Adv Musculoskelet Dis 2014; 6(4):144-53.
  • Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: Structure, composition, and function. Sports Health 2009; 1(6):461-8.
  • Dinarello CA. Proinflammatory cytokines. Chest 2000; 118(2):503-8.
  • Mabey T, Honsawek S. Cytokines as biochemical markers for knee osteoarthritis. World J Orthop 2015; 6(1):95-105.
  • Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7(1):33-42.
  • Tsuchida AI, Beekhuizen M, Hart MC, Radstake TR, Dhert WJ, Saris DB, van Osch GJ, Creemers LB. Cyto- kine profiles in the joint depend on pathology, but are different between synovial fluid, cartilage tissue and cultu- red chondrocytes. Arthritis Res Ther 2014; 16(5):441.
  • Orita S, Koshi T, Mitsuka T, Miyagi M, Inoue G, Arai G, Ishikawa T, Hanaoka E, Yamashita K, Yamashita M, Eguchi Y, Toyone T, Takahashi K, Ohtori S. Associa- tions between proinflammatory cytokines in the synovial fluid and radiographic grading and pain-related scores in 47 consecutive patients with osteoarthritis of the knee. BMC Musculoskelet Disord 2011; 12:144.
  • Rigoglou S, Papavassiliou AG. The NF-kappaB signalling pathway in osteoarthritis. Int J Biochem Cell Biol 2013; 45(11):2580-4.
  • Saetan N, Honsawek S, Tanavalee A, Tantavisut S, Yuktanandana P, Parkpian V. Association of plasma and synovial fluid interferon-gamma inducible protein-10 with radiographic severity in knee osteoarthritis. Clin Biochem 2011; 44(14-15):1218-22.
  • Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957; 16(4):494-502.
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25(4):402-8.
  • Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012; 9(7):671-5.
  • Hame SL, Alexander RA. Knee osteoarthritis in women. Curr Rev Musculoskelet Med 2013; 6(2):182-7.
  • Jafarzadeh SR, Felson DT. Updated estimates suggest a much higher prevalence of arthritis in United States Adults Than Previous Ones. Arthritis Rheumatol 2018; 70(2):185-92.
  • Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, Dragomir A, Kalsbeek WD, Luta G, Jordan JM. Lifetime risk of symptomatic knee osteoarthri- tis. Arthritis Rheum 2008; 59(9):1207-13.
  • Kaufman KR, Hughes C, Morrey BF, Morrey M, An KN. Gait characteristics of patients with knee osteoarthri- tis. J Biomech 2001; 34(7):907-15.
  • Rahmati M, Mobasheri A, Mozafari M. Inflammatory mediators in osteoarthritis: A critical review of the state- of-the-art, current prospects, and future challenges. Bone 2016; 85:81-90.
  • Pearle AD, Scanzello CR, George S, Mandl LA, DiCarlo EF, Peterson M, Sculco TP, Crow MK. Elevated high- sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthritis Cartilage 2007; 15(5):516-23.
  • Sturmer T, Brenner H, Koenig W, Gunther KP. Seve- rity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Ann Rheum Dis 2004; 63(2):200-5.
  • Uson J, Balsa A, Pascual-Salcedo D, Cabezas JA, Gonza- lez-Tarrio JM, Martin-Mola E, Fontan G. Soluble inter- leukin 6 (IL-6) receptor and IL-6 levels in serum and syno- vial fluid of patients with different arthropathies. J Rheu- matol 1997; 24(11):2069-75.
  • Mohr S, Liew CC. The peripheral-blood transcriptome: New insights into disease and risk assessment. Trends Mol Med 2007; 13(10):422-32.
  • Ling SM, Patel DD, Garnero P, Zhan M, Vaduganathan M, Muller D, Taub D, Bathon JM, Hochberg M, Aber- nethy DR, Metter EJ, Ferrucci L. Serum protein signatu- res detect early radiographic osteoarthritis. Osteoarthritis Cartilage 2009; 17(1):43-8.
  • Gu C, Wu L, Li X. IL-17 family: Cytokines, receptors and signaling. Cytokine 2013; 64(2):477-85.
  • Shahrara S, Pickens SR, Mandelin AM, 2nd, Karpus WJ, Huang Q, Kolls JK, Pope RM. IL-17-mediated monocyte migration occurs partially through CC chemokine ligand 2/monocyte chemoattractant protein-1 induction. J Immunol 2010; 184(8):4479-87.
  • Snelling SJ, Bas S, Puskas GJ, Dakin SG, Suva D, Finckh A, Gabay C, Hoffmeyer P, Carr AJ, Lubbeke A. Presence of IL-17 in synovial fluid identifies a potential inflammatory osteoarthritic phenotype. PLoS One 2017; 12(4):e0175109.
  • Chen B, Deng Y, Tan Y, Qin J, Chen LB. Association between severity of knee osteoarthritis and serum and synovial fluid interleukin 17 concentrations. J Int Med Res 2014; 42(1):138-44.
  • Tanaka K, Itoh S, Shimizu N. Structure and regulation of expression of corticotropin-releasing hormone (CRH) gene and processing of CRH-precursor. Nihon Rinsho 1989; 47(10):2146-51.
  • Wang K, Xu J, Cai J, Zheng S, Yang X, Ding C. Serum levels of resistin and interleukin-17 are associated with increased cartilage defects and bone marrow lesions in patients with knee osteoarthritis. Mod Rheumatol 2017; 27(2):339-44.
  • Zhang X, Yuan Y, Pan Z, Ma Y, Wu M, Yang J, Han R, Chen M, Hu X, Liu R, Sam NB, Xu S, Pan F. Eleva- ted circulating IL-17 level is associated with inflammatory arthritis and disease activity: A meta-analysis. Clin Chim Acta 2019; 496:76-83.
  • Wang Z, Zheng C, Zhong Y, He J, Cao X, Xia H, Ba H, Li P, Wu S, Peng C. Interleukin-17 can induce oste- oarthritis in rabbit knee joints similar to Hulth’s Method. Biomed Res Int 2017; 2017:2091325.
  • Cheng W, Wu D, Zuo Q, Wang Z, Fan W. Ginseno- side Rb1 prevents interleukin-1 beta induced inflamma- tion and apoptosis in human articular chondrocytes. Int Orthop 2013; 37(10):2065-70.
  • Yang B, Kang X, Xing Y, Dou C, Kang F, Li J, Quan Y, Dong S. Effect of microRNA-145 on IL-1beta-induced cartilage degradation in human chondrocytes. FEBS Lett 2014; 588(14):2344-52.
  • Qiu B, Gong M, He QT, Zhou PH. Controlled Release of Interleukin-1 Receptor Antagonist from Hyaluronic Acid- Chitosan Microspheres Attenuates Interleukin-1beta- Induced Inflammation and Apoptosis in Chondrocytes. Biomed Res Int 2016; 2016:6290957.
  • Bender S, Haubeck HD, Van de Leur E, Dufhues G, Schiel X, Lauwerijns J, Greiling H, Heinrich PC. Interleu- kin-1 beta induces synthesis and secretion of interleukin-6 in human chondrocytes. FEBS Lett 1990; 263(2):321-4.
  • Wojdasiewicz P, Poniatowski LA, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm 2014; 2014:561459.
  • Kwan Tat S, Padrines M, Theoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF-alpha/IL-1: Interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev 2004; 15(1):49-60.
  • Chenoufi HL, Diamant M, Rieneck K, Lund B, Stein GS, Lian JB. Increased mRNA expression and protein secretion of interleukin-6 in primary human osteoblasts differentiated in vitro from rheumatoid and osteoarthritic bone. J Cell Biochem 2001; 81(4):666-78.
  • Poree B, Kypriotou M, Chadjichristos C, Beauchef G, Renard E, Legendre F, Melin M, Gueret S, Hartmann DJ, Mallein-Gerin F, Pujol JP, Boumediene K, Galera P. Interleukin-6 (IL-6) and/or soluble IL-6 receptor down- regulation of human type II collagen gene expression in articular chondrocytes requires a decrease of Sp1.Sp3 ratio and of the binding activity of both factors to the COL2A1 promoter. J Biol Chem 2008; 283(8):4850-65.

Investigation of the Proinflammatory Cytokines’ Effects in Peripheral Blood and Cartilage Tissue Samples of Knee Osteoarthritis Patients

Year 2020, Volume: 6 Issue: 3, 373 - 381, 01.01.2020

Abstract

Objective: Osteoarthritis OA is a degenerative joint disease that results in pain and dysfunction. Cytokines, which are regulatory molecules in the metabolism with roles in the pathophysiology of OA, are important factors investigated regarding diagnosis and treatment. The aim of this study was to demonstrate the association between IL-1β, IL-6, IL-17, IL-18 and TNF-α proinflammatory cytokines and OA, and to identify the imbalanced catabolic activity in cartilage tissue. We also aimed to determine possible biomarker candidates for diagnosis and treatment processes by comparing cytokines in serum and cartilage Material and Methods: Western blotting was performed to determine protein levels, and quantitative real-time polymerase chain reaction was performed to determine the gene expression levels of cytokines in the blood and tissue samples taken from patient and control groups for a total of 30 cases. The C-reactive protein CRP levels and Kellgren-Lawrence K-L scoring of patients were also investigated. Results: As regards protein levels, the level of IL-6 in tissue, and of IL-1β and IL-17 in blood were found to be statistically significant p

References

  • Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr AJ. Osteoarthritis. Lancet 2015; 386(9991):376-87.
  • Mobasheri A, Batt M. An update on the pathophysio- logy of osteoarthritis. Ann Phys Rehabil Med 2016; 59(5- 6):333-9.
  • Hosnijeh FS, Runhaar J, van Meurs JB, Bierma-Zeins- tra SM. Biomarkers for osteoarthritis: Can they be used for risk assessment? A systematic review. Maturitas 2015; 82(1):36-49.
  • Ishijima M, Kaneko H, Kaneko K. The evolving role of biomarkers for osteoarthritis. Ther Adv Musculoskelet Dis 2014; 6(4):144-53.
  • Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: Structure, composition, and function. Sports Health 2009; 1(6):461-8.
  • Dinarello CA. Proinflammatory cytokines. Chest 2000; 118(2):503-8.
  • Mabey T, Honsawek S. Cytokines as biochemical markers for knee osteoarthritis. World J Orthop 2015; 6(1):95-105.
  • Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7(1):33-42.
  • Tsuchida AI, Beekhuizen M, Hart MC, Radstake TR, Dhert WJ, Saris DB, van Osch GJ, Creemers LB. Cyto- kine profiles in the joint depend on pathology, but are different between synovial fluid, cartilage tissue and cultu- red chondrocytes. Arthritis Res Ther 2014; 16(5):441.
  • Orita S, Koshi T, Mitsuka T, Miyagi M, Inoue G, Arai G, Ishikawa T, Hanaoka E, Yamashita K, Yamashita M, Eguchi Y, Toyone T, Takahashi K, Ohtori S. Associa- tions between proinflammatory cytokines in the synovial fluid and radiographic grading and pain-related scores in 47 consecutive patients with osteoarthritis of the knee. BMC Musculoskelet Disord 2011; 12:144.
  • Rigoglou S, Papavassiliou AG. The NF-kappaB signalling pathway in osteoarthritis. Int J Biochem Cell Biol 2013; 45(11):2580-4.
  • Saetan N, Honsawek S, Tanavalee A, Tantavisut S, Yuktanandana P, Parkpian V. Association of plasma and synovial fluid interferon-gamma inducible protein-10 with radiographic severity in knee osteoarthritis. Clin Biochem 2011; 44(14-15):1218-22.
  • Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957; 16(4):494-502.
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25(4):402-8.
  • Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012; 9(7):671-5.
  • Hame SL, Alexander RA. Knee osteoarthritis in women. Curr Rev Musculoskelet Med 2013; 6(2):182-7.
  • Jafarzadeh SR, Felson DT. Updated estimates suggest a much higher prevalence of arthritis in United States Adults Than Previous Ones. Arthritis Rheumatol 2018; 70(2):185-92.
  • Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, Dragomir A, Kalsbeek WD, Luta G, Jordan JM. Lifetime risk of symptomatic knee osteoarthri- tis. Arthritis Rheum 2008; 59(9):1207-13.
  • Kaufman KR, Hughes C, Morrey BF, Morrey M, An KN. Gait characteristics of patients with knee osteoarthri- tis. J Biomech 2001; 34(7):907-15.
  • Rahmati M, Mobasheri A, Mozafari M. Inflammatory mediators in osteoarthritis: A critical review of the state- of-the-art, current prospects, and future challenges. Bone 2016; 85:81-90.
  • Pearle AD, Scanzello CR, George S, Mandl LA, DiCarlo EF, Peterson M, Sculco TP, Crow MK. Elevated high- sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthritis Cartilage 2007; 15(5):516-23.
  • Sturmer T, Brenner H, Koenig W, Gunther KP. Seve- rity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Ann Rheum Dis 2004; 63(2):200-5.
  • Uson J, Balsa A, Pascual-Salcedo D, Cabezas JA, Gonza- lez-Tarrio JM, Martin-Mola E, Fontan G. Soluble inter- leukin 6 (IL-6) receptor and IL-6 levels in serum and syno- vial fluid of patients with different arthropathies. J Rheu- matol 1997; 24(11):2069-75.
  • Mohr S, Liew CC. The peripheral-blood transcriptome: New insights into disease and risk assessment. Trends Mol Med 2007; 13(10):422-32.
  • Ling SM, Patel DD, Garnero P, Zhan M, Vaduganathan M, Muller D, Taub D, Bathon JM, Hochberg M, Aber- nethy DR, Metter EJ, Ferrucci L. Serum protein signatu- res detect early radiographic osteoarthritis. Osteoarthritis Cartilage 2009; 17(1):43-8.
  • Gu C, Wu L, Li X. IL-17 family: Cytokines, receptors and signaling. Cytokine 2013; 64(2):477-85.
  • Shahrara S, Pickens SR, Mandelin AM, 2nd, Karpus WJ, Huang Q, Kolls JK, Pope RM. IL-17-mediated monocyte migration occurs partially through CC chemokine ligand 2/monocyte chemoattractant protein-1 induction. J Immunol 2010; 184(8):4479-87.
  • Snelling SJ, Bas S, Puskas GJ, Dakin SG, Suva D, Finckh A, Gabay C, Hoffmeyer P, Carr AJ, Lubbeke A. Presence of IL-17 in synovial fluid identifies a potential inflammatory osteoarthritic phenotype. PLoS One 2017; 12(4):e0175109.
  • Chen B, Deng Y, Tan Y, Qin J, Chen LB. Association between severity of knee osteoarthritis and serum and synovial fluid interleukin 17 concentrations. J Int Med Res 2014; 42(1):138-44.
  • Tanaka K, Itoh S, Shimizu N. Structure and regulation of expression of corticotropin-releasing hormone (CRH) gene and processing of CRH-precursor. Nihon Rinsho 1989; 47(10):2146-51.
  • Wang K, Xu J, Cai J, Zheng S, Yang X, Ding C. Serum levels of resistin and interleukin-17 are associated with increased cartilage defects and bone marrow lesions in patients with knee osteoarthritis. Mod Rheumatol 2017; 27(2):339-44.
  • Zhang X, Yuan Y, Pan Z, Ma Y, Wu M, Yang J, Han R, Chen M, Hu X, Liu R, Sam NB, Xu S, Pan F. Eleva- ted circulating IL-17 level is associated with inflammatory arthritis and disease activity: A meta-analysis. Clin Chim Acta 2019; 496:76-83.
  • Wang Z, Zheng C, Zhong Y, He J, Cao X, Xia H, Ba H, Li P, Wu S, Peng C. Interleukin-17 can induce oste- oarthritis in rabbit knee joints similar to Hulth’s Method. Biomed Res Int 2017; 2017:2091325.
  • Cheng W, Wu D, Zuo Q, Wang Z, Fan W. Ginseno- side Rb1 prevents interleukin-1 beta induced inflamma- tion and apoptosis in human articular chondrocytes. Int Orthop 2013; 37(10):2065-70.
  • Yang B, Kang X, Xing Y, Dou C, Kang F, Li J, Quan Y, Dong S. Effect of microRNA-145 on IL-1beta-induced cartilage degradation in human chondrocytes. FEBS Lett 2014; 588(14):2344-52.
  • Qiu B, Gong M, He QT, Zhou PH. Controlled Release of Interleukin-1 Receptor Antagonist from Hyaluronic Acid- Chitosan Microspheres Attenuates Interleukin-1beta- Induced Inflammation and Apoptosis in Chondrocytes. Biomed Res Int 2016; 2016:6290957.
  • Bender S, Haubeck HD, Van de Leur E, Dufhues G, Schiel X, Lauwerijns J, Greiling H, Heinrich PC. Interleu- kin-1 beta induces synthesis and secretion of interleukin-6 in human chondrocytes. FEBS Lett 1990; 263(2):321-4.
  • Wojdasiewicz P, Poniatowski LA, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm 2014; 2014:561459.
  • Kwan Tat S, Padrines M, Theoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF-alpha/IL-1: Interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev 2004; 15(1):49-60.
  • Chenoufi HL, Diamant M, Rieneck K, Lund B, Stein GS, Lian JB. Increased mRNA expression and protein secretion of interleukin-6 in primary human osteoblasts differentiated in vitro from rheumatoid and osteoarthritic bone. J Cell Biochem 2001; 81(4):666-78.
  • Poree B, Kypriotou M, Chadjichristos C, Beauchef G, Renard E, Legendre F, Melin M, Gueret S, Hartmann DJ, Mallein-Gerin F, Pujol JP, Boumediene K, Galera P. Interleukin-6 (IL-6) and/or soluble IL-6 receptor down- regulation of human type II collagen gene expression in articular chondrocytes requires a decrease of Sp1.Sp3 ratio and of the binding activity of both factors to the COL2A1 promoter. J Biol Chem 2008; 283(8):4850-65.
There are 41 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Sezen Atasoy This is me

Publication Date January 1, 2020
Published in Issue Year 2020 Volume: 6 Issue: 3

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Vancouver Atasoy S. Diz Osteoartrit Hastalarının Periferik Kan ve Kıkırdak Doku Örneklerinde Proinflamatuvar Sitokinlerin Etkilerinin Araştırılması. Akd Med J. 2020;6(3):373-81.