[논문]Modulation of Apoptosis and Differentiation by the Treatment of Sulfasalazine in Rabbit Articular Chondrocytes

Lee, Won Kil; Kang, Jin Seok

doi:10.5487/tr.2016.32.2.115

Modulation of Apoptosis and Differentiation by the Treatment of Sulfasalazine in Rabbit Articular Chondrocytes 원문보기

Toxicological research, v.32 no.2, 2016년, pp.115 - 121

Lee, Won Kil (Department of Biomedical Laboratory Science, Namseoul University) , Kang, Jin Seok (Department of Biomedical Laboratory Science, Namseoul University)

Abstract ▼ AI-Helper

This study was conducted to examine the cellular regulatory mechanisms of sulfasalazine (SSZ) in rabbit articular chondrocytes treated with sodium nitroprusside (SNP). Cell phenotype was determined, and the MTT assay, Western blot analysis and immunofluorescence staining of type II collagen was performed in control, SNP-treated and SNP plus SSZ ($50{\sim}200{\mu}g/mL$) rabbit articular chondrocytes. Cellular proliferation was decreased significantly in the SNP-treated group compared with that in the control (p < 0.01). SSZ treatment clearly increased the SNP-reduced proliferation levels in a concentration-dependent manner (p < 0.01). SNP treatment induced significant dedifferentiation and inflammation compared with control chondrocytes (p < 0.01). Type II collagen expression levels increased in a concentration-dependent manner in response to SSZ treatment but were unaltered in SNP-treated chondrocytes (p < 0.05 and < 0.01, respectively). Cylooxygenase-2 (COX-2) expression increased in a concentration-dependent manner in response to SSZ treatment but was unaltered in SNP-treated chondrocytes (p < 0.05). Immunofluorescence staining showed that SSZ treatment increased type II collagen expression compared with that in SNP-treated chondrocytes. Furthermore, phosphorylated extracellular regulated kinase (pERK) expression levels were decreased significantly in the SNP-treated group compared with those in control chondrocytes (p < 0.01). Expression levels of pERK increased in a concentration-dependent manner by SSZ but were unaltered in SNP-treated chondrocytes. pp38 kinase expression levels increased in a concentration-dependent manner by SSZ but were unaltered in control chondrocytes (p < 0.01). In summary, SSZ significantly inhibited nitric oxide-induced cell death and dedifferentiation, and regulated extracellular regulated kinases 1 and 2 and p38 kinase in rabbit articular chondrocytes.

주제어

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문제 정의

However, the molecular mechanism of cartilage degeneration is largely unknown (5,19,20). The aim of this study was to understand the basic molecular mechanism of cartilage degeneration, which is important for therapy in patients with degenerative cartilage disease.
The purpose of this study was to examine the RA cellular regulatory mechanisms via SSZ in rabbit articular chondrocytes. Other studies have provided cell signaling information by identifying the cellular control mechanisms.

제안 방법

Statistical analyses were performed using GraphPad Prism 6 (GraphPad Software, La Jolla, CA, USA). All data were analyzed using Student’s t-test and are expressed as the mean ± standard deviation.

데이터처리

All data were analyzed using Student’s t-test and are expressed as the mean ± standard deviation.

이론/모형

1A). To investigate the role of SSZ in chondrocyte proliferation, cells were treated with SSZ and proliferation measured using the MTT assay. The level of cell proliferation decreased significantly in response to SNP treatment as compared with that in the control (p < 0.

참고문헌 (49)

1 Hadjigogos K 2003 The role of free radicals in the pathogenesis of rheumatoid arthritis Panminerva Med 45 7 13 12682616

상세보기
2 Harris ED Jr Faulkner CS 2nd Brown FE 1975 Collagenolytic systems in rheumatoid arthritis Clin Orthop Relat Res 110 303 316 10.1097/00003086-197507000-00041 168997

상세보기
3 Dai SM Shan ZZ Xu H Nishioka K 2007 Cellular targets of interleukin-18 in rheumatoid arthritis Ann Rheum Dis 66 1411 1418 10.1136/ard.2006.067793 2111635 --> 17502360

상세보기
4 Otero M Goldring MB 2007 Cells of the synovium in rheumatoid arthritis Arthritis Res Ther 9 220 10.1186/ar2292 18001488

상세보기
5 Scott DL Wolfe F Huizinga TW 2010 Rheumatoid arthritis Lancet 376 1094 1108 10.1016/S0140-6736(10)60826-4 20870100

상세보기
6 Abramson SB Amin A 2002 Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage Rheumatology (Oxford) 41 972 980 10.1093/rheumatology/41.9.972 12209029

상세보기
7 Carrillo Gutiérrez OY Pérez Sánchez AG Medina Serriteño N Rodríguez Orozco AR 2007 Side effects of COX-2 selective inhibitors. Critic related with its administration in patients with rheumatoid arthritis and osteoarthritis Rev Alerg Mex 54 116 122 18297851
8 Chen YF Jobanputra P Barton P Bryan S Fry-Smith A Harris G Taylor RS 2008 Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation Health Technol Assess 12 1 278 10.3310/hta12110 18405470

상세보기
9 Shiozawa S Tokuhisa T 1992 Contribution of synovial mesenchymal cells to the pathogenesis of rheumatoid arthritis Semin Arthritis Rheum 21 267 273 10.1016/0049-0172(92)90058-L 1570520

상세보기
10 Tutuncu Z Kavanaugh A 2007 Rheumatic disease in the elderly: rheumatoid arthritis Rheum Dis Clin North Am 33 57 70 10.1016/j.rdc.2006.12.006 17367692

상세보기
11 Vergunst CE van de Sande MG Lebre MC Tak PP 2005 The role of chemokines in rheumatoid arthritis and osteoarthritis Scand J Rheumatol 34 415 425 10.1080/03009740500439159 16393761

상세보기
12 Combe B 1998 Inflammation and joint destruction during rheumatoid polyarthritis: what relation? Presse Med 27 481 483 9767983
13 Häuselmann HJ 1997 Mechanisms of cartilage destruction and novel nonsurgical therapeutic strategies to retard cartilage injury in rheumatoid arthritis Curr Opin Rheumatol 9 241 250 10.1097/00002281-199705000-00011 9204260

상세보기
14 Meyer O 2000 Role of anti-TNF therapy in rheumatoid arthritis Presse Med 29 463 468 10745935
15 Reines BP 2004 Is rheumatoid arthritis premature osteoarthritis with fetal-like healing? Autoimmun Rev 3 305 311 10.1016/j.autrev.2003.11.002 15246027

상세보기
16 Kastrinaki MC Papadaki HA 2009 Mesenchymal stromal cells in rheumatoid arthritis: biological properties and clinical applications Curr Stem Cell Res Ther 4 61 69 10.2174/157488809787169084 19149631

상세보기
17 Lombardi A Pignone A Perfetto F Tarquini R Partsch G Matucci-Cerinic M 1993 The enzymatic mechanisms involved in the pathogenesis of rheumatoid arthritis and arthrosis. The role of metalloproteases and serine proteases in the breakdown of articular cartilage Recenti Prog Med 84 634 641 8210629
18 Shiozawa S Shiozawa K 1988 A review of the histopathological evidence on the pathogenesis of cartilage destruction in rheumatoid arthritis Scand J Rheumatol Suppl 74 65 72 10.3109/03009748809102940 3068794

상세보기
19 Bouffi C Djouad F Mathieu M Noël D Jorgensen C 2009 Multipotent mesenchymal stromal cells and rheumatoid arthritis: risk or benefit? Rheumatology (Oxford) 48 1185 1189 10.1093/rheumatology/kep162 19561159

상세보기
20 Magliano M 2008 Obesity and arthritis Menopause Int 14 149 154 19037063

상세보기
21 Amin AR Abramson SB 1998 The role of nitric oxide in articular cartilage breakdown in osteoarthritis Curr Opin Rheumatol 10 263 268 10.1097/00002281-199805000-00018 9608331

상세보기
22 Martel-Pelletier J Alaaeddine N Pelletier JP 1999 Cytokines and their role in the pathophysiology of osteoarthritis Front Biosci 4 D694 D703 10.2741/Martel 10525480

상세보기
23 Blanco FJ Guitian R Vázquez-Martul E de Toro FJ Galdo F 1998 Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology Arthritis Rheum 41 284 289 10.1002/1529-0131(199802)41:2 3.0.CO;2-T 9485086

상세보기
24 Hashimoto S Ochs RL Komiya S Lotz M 1998 Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis Arthritis Rheum 41 1632 1638 10.1002/1529-0131(199809)41:9 3.0.CO;2-A 9751096

상세보기
25 Yatsugi N Tsukazaki T Osaki M Koji T Yamashita S Shindo H 2000 Apoptosis of articular chondrocytes in rheumatoid arthritis and osteoarthritis: correlation of apoptosis with degree of cartilage destruction and expression of apoptosis-related proteins of p53 and c-myc J Orthop Sci 5 150 156 10.1007/s007760050142 10982649

상세보기
26 Cao M Westerhausen-Larson A Niyibizi C Kavalkovich K Georgescu HI Rizzo CF Hebda PA Stefanovic-Racic M Evans CH 1997 Nitric oxide inhibits the synthesis of type-II collagen without altering Col2A1 mRNA abundance: prolyl hydroxylase as a possible target Biochem J 324 305 310 10.1042/bj3240305 1218431 --> 9164871

상세보기
27 Taskiran D Stefanovic-Racic M Georgescu H Evans C 1994 Nitric oxide mediates suppression of cartilage proteoglycan synthesis by interleukin-1 Biochem Biophys Res Commun 200 142 148 10.1006/bbrc.1994.1426 7513156

상세보기
28 Kim SJ Hwang SG Shin DY Kang SS Chun JS 2002 p38 kinase regulates nitric oxide-induced apoptosis of articular chondrocytes by accumulating p53 via NFκB-dependent transcription and stabilization by serine 15 phosphorylation J Biol Chem 277 33501 33508 10.1074/jbc.M202862200 12091386

상세보기
29 Kim SJ Ju JW Oh CD Yoon YM Song WK Kim JH Yoo YJ Bang OS Kang SS Chun JS 2002 ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status J Biol Chem 277 1332 1339 10.1074/jbc.M107231200 11689560

상세보기
30 Kim SJ Kim HG Oh CD Hwang SG Song WK Yoo YJ Kang SS Chun JS 2002 p38 kinase-dependent and -independent Inhibition of protein kinase C ζ and -α regulates nitric oxide-induced apoptosis and dedifferentiation of articular chondrocytes J Biol Chem 277 30375 30381 10.1074/jbc.M205193200 12048219

상세보기
31 Klotz U 1985 Clinical efficacy of oral 5-aminosalicylic acid in the treatment of inflammatory bowel disease Am J Gastroenterol 80 660 4025285

상세보기
32 Peppercorn MA 1984 Sulfasalazine. Pharmacology, clinical use, toxicity, and related new drug development Ann Intern Med 101 377 386 10.7326/0003-4819-101-3-377 6147110

상세보기
33 Astbury C Taggart AJ Juby L Zebouni L Bird HA 1990 Comparison of the single dose pharmacokinetics of sulphasalazine in rheumatoid arthritis and inflammatory bowel disease Ann Rheum Dis 49 587 590 10.1136/ard.49.8.587 1004169 --> 1975737

상세보기
34 Plosker GL Croom KF 2005 Sulfasalazine: a review of its use in the management of rheumatoid arthritis Drugs 65 1825 1849 10.2165/00003495-200565130-00008 16114981

상세보기
35 Azadkhan AK Truelove SC Aronson JK 1982 The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man Br J Clin Pharmacol 13 523 528 10.1111/j.1365-2125.1982.tb01415.x 1402052 --> 6121576

상세보기
36 Klotz U Schwab M 2005 Topical delivery of therapeutic agents in the treatment of inflammatory bowel disease Adv Drug Deliv Rev 57 267 279 10.1016/j.addr.2004.08.007 15555742

상세보기
37 Friedman G 1986 Sulfasalazine and new analogues Am J Gastroenterol 81 141 144 2868653

상세보기
38 Klotz U 1985 Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid Clin Pharmacokinet 10 285 302 10.2165/00003088-198510040-00001 2864155

상세보기
39 van Hees PA Bakker JH van Tongeren JH 1980 Effect of sulphapyridine, 5-aminosalicylic acid, and placebo in patients with idiopathic proctitis: a study to determine the active therapeutic moiety of sulphasalazine Gut 21 632 635 10.1136/gut.21.7.632 1419886 --> 6107263

상세보기
40 Yazdanian M Glynn SL Wright JL Hawi A 1998 Correlating partitioning and Caco-2 cell permeability of structurally diverse small molecular weight compounds Pharm Res 15 1490 1494 10.1023/A:1011930411574 9755906

상세보기
41 Yoon YM Kim SJ Oh CD Ju JW Song WK Yoo YJ Huh TL Chun JS 2002 Maintenance of differentiated phenotype of articular chondrocytes by protein kinase C and extracellular signal-regulated protein kinase J Biol Chem 277 8412 8420 10.1074/jbc.M110608200 11744731

상세보기
42 Ryu JH Kim SJ Kim SH Oh CD Hwang SG Chun CH Oh SH Seong JK Huh TL Chun JS 2002 Regulation of the chondrocyte phenotype by β-catenin Development 129 5541 5550 10.1242/dev.00110 12403723

상세보기
43 Poole AR 2003 Cartilage in health and disease in Arthritis and Allied Conditions McCarthy DJ Koopman WJ Lea and Febiger Philadelphia 279 333
44 Goldring MB Birkhead J Sandell LJ Kimura T Krane SM 1988 Interleukin 1 suppresses expression of cartilage-specific types II and IX collagens and increases types I and III collagens in human chondrocytes J Clin Invest 82 2026 2037 10.1172/JCI113823 442785 --> 3264290

상세보기
45 Benya PD Padilla SR Nimni ME 1978 Independent regulation of collagen types by chondrocytes during the loss of differentiated function in culture Cell 15 1313 1321 10.1016/0092-8674(78)90056-9 729001

상세보기
46 Gay S Gay RE Koopman WJ 1993 Molecular and cellular mechanisms of joint destruction in rheumatoid arthritis: two cellular mechanisms explain joint destruction? Ann Rheum Dis 52 S39 S47 10.1136/ard.52.Suppl_1.S39 1035025 --> 8481058

상세보기
47 Sandell LJ Aigner T 2001 Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis Arthritis Res 3 107 113 10.1186/ar148 128887 --> 11178118

상세보기
48 Myers LK Kang AH Postlethwaite AE Rosloniec EF Morham SG Shlopov BV Goorha S Ballou LR 2000 The genetic ablation of cyclooxygenase 2 prevents the development of autoimmune arthritis Arthritis Rheum 43 2687 2693 10.1002/1529-0131(200012)43:12 3.0.CO;2-9 11145026

상세보기
49 Oh CD Chang SH Yoon YM Lee SJ Lee YS Kang SS Chun JS 2000 Opposing role of mitogen-activated protein kinase subtypes, erk-1/2 and p38, in the regulation of chondrogenesis of mesenchymes J Biol Chem 275 5613 5619 10.1074/jbc.275.8.5613 10681543

상세보기

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