骨桥蛋白在类风湿关节炎发病机理中的研究进展

摘要/Abstract

摘要： 类风湿关节炎是一种严重影响病人生活质量的重大自身免疫性疾病,但其致病原因和发病机制至今尚不清楚。骨桥蛋白是一种细胞外基质蛋白,包含RGD(Arg-Gly-Asp)序列,被认为是一种促炎因子。研究发现骨桥蛋白是引发类风湿关节炎的重要因素,其在骨质代谢及免疫系统中具有双重作用,本文综述了骨桥蛋白对类风湿关节炎发病机理的影响。

关键词: 骨桥蛋白, 类风湿关节炎, 促炎因子

Abstract: Rheumatoid arthritis is one of the most critical diseases that impair the quality of patients’life,but its pathogenesis has not yet been fully understood. Osteopontin (OPN) is an extracellular matrix protein containing Arg-Gly-Asp (RGD) sequence and has been recently recognized as a potential inflammatory cytokine. It is discovered that OPN plays an important role in the pathogenesis of rheumatoid arthritis. It is a bridge between bone and the immune system. This paper reviewed the pivotal role that OPN plays in the pathogenesis of rheumatoid arthritis.

Key words: osteopontin, rheumatoid arthritis, proinflammatory cytokine

中图分类号:

R593.22

张鸽, 吴玉林. 骨桥蛋白在类风湿关节炎发病机理中的研究进展[J]. 中国临床药理学与治疗学, 2007, 12(5): 488-492.

ZHANG Ge, WU Yu-lin. Research advances of osteopontin in pathogenesis of rheumatoid arthritis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(5): 488-492.

参考文献

1 Szekanecz Z, Kim J, Koch AE.Chemokines and chemokine receptors in rheumatoid arthritis[J].Semin Immunol, 2003;15:15-21.
2 Genovese MC, Bathon JM, Martin RW, et al.Etanercept ver- sus methotrexate in patients with early rheumatoid arthritis:twoyear radiographic and clinical outcomes[J].Arthritis Rheum, 2002;46:1443-1450.
3 Chabas D, Baranzini SE, Mitchell D, et al.The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease[J].Science, 2001 ;294:1731-1735.
4 Vogt MH, Lopatinskaya L, Smits M, et al.Elevated osteopontin levels in active relapsing-remitting multiple sclerosis[J].Ann Neurol, 2003;53:819-822.
5 Petrow PK, Hummel KM, Schedel J, et al.Expression of osteopontin messenger RNA and protein in rheumatoid arthritis:effects of osteopontin on the release of collagenase 1 from articular chondrocytes and synovial fibroblasts[J].Arthritis Rheum, 2000;43:1597-1605.
6 Mimura S, Mochida S, Inao M, et al.Massive liver necrosis after provocation of imbalance between Th1 and Th2 immune reactions in osteopontin transgenic mice [J].J Gastroenterol, 2004;39:867-872.
7 Gravallese EM.Osteopontin:a bridge between bone and the immune system[J].J Clin Invest, 2003;112:147-149.
8 宁江海.细胞外基质蛋白与骨损伤修复[J].国外医学:口腔医学分册, 2000 ;27:41-44.
9 Yumoto K, Ishijima M, Rittling SR, et al.Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice[J].Proc Natl Acad Sci USA,2002;99:4556-4561.
10 Ashkar S, Weber GF, Panoutsakopoulou V, et al.Eta-1 ( osteopontin):an early component of type-1 ( cell-mediated) immunity[J].Science, 2000 ;287:860-864.
11 Gravallese EM, Manning C, Tsay A, et al.Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor [J].Arthritis Rheum, 2000 ;43:250-258.
12 Miyamoto T, Arai F, Ohneda O, et al.An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B ligand[J].Blood, 2000;96:4335-4343.
13 Ihara H, Denhardt DT, Furuy a K, et al.Parathy roid hormoneinduced bone resorption does not occur in the absence of osteopontin[J].J Biol Chem, 2001 ;276:13065-13071.
14 Ohshima S, Kobayashi H, Yamaguchi N, et al.Expression of osteopontin at sites of bone erosion in a murine experimental arthritis model of collagen-induced arthritis:possible involvement of osteopontin in bone destruction in arthritis[J].Arthritis Rheum, 2002 ;46:1094-1101.
15 Badger AM, Blake S, Kapadia R, et al.Disease-modifying activity of SB 273005, an orally active, nonpeptide alphavbeta3 ( vitronectin receptor) antagonist, in rat adjuvant-induced arthritis[J].Arthritis Rheum, 2001 ;44:128-137.
16 Storgard CM, Stupack DG, Jonczyk A, et al.Decreased angiogenesis and arthritic disease in rabbits treated with an alphavbeta3 antagonist[J].J Clin Invest, 1999;103:47-54.
17 Yamamoto N, Sakai F, Kon S, et al.Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis[J].J Clin Invest, 2003 ;112:181-188.
18 Ohshima S, Yamaguchi N, Nishioka K, et al.Enhanced local production of osteopontin in rheumatoid joints[J].J Rheumatol, 2002 ;29:2061-2067.
19 Guo H, Cai CQ, Schroeder RA, et al.Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages[J].J Immunol, 2001;166:1079-1086.
20 Jacobs JP, Pettit AR, Shinohara ML, et al.Lack of requirement of osteopontin for inflammation, bone erosion, and cartilage damage in the K B×N model of autoantibody-mediated arthritis[J].Arthritis Rheum, 2004;50:2685-2694.
21 Mazzali M, Kipari T, Ophascharoensuk V, et al.Osteopontina molecule for all seasons[J].QJM, 2002;95:3-13.
22 Xu G, Sun W, He D, et al.Overexpression of osteopontin in rheumatoid synovial mononuclear cells is associated with joint inflammation, not with genetic polymorphism[J].J Rheumatol,2005 ;32:410-416.
23 D′Alfonso S, Barizzone N, Giordano M, et al.Two single-nucleotide polymorphisms in the 5′and 3′ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus [J].Arthritis Rheum, 2005;52:539-547.
24 Xu G, Nie H, Li N, et al.Role of osteopontin in amplification and perpetuation of rheumatoid synovitis[J].J Clin Invest, 2005 ;115:1060-1067.
25 Urcelay E, Martinez A, Mas-Fontao A, et al.Osteopontin gene polymorphisms in Spanish patients with rheumatoid arthritis[J].J Rheumatol, 2005;32:405-409.
26 夏丽娟, 陈飞虎, 黄学应, 等.重组人内抑素对佐剂性关节炎大鼠滑膜组织血管内皮细胞生长因子表达的影响[J].中国临床药理学与治疗学, 2006;11:760-763.
27 Gattorno M, Gregorio A, Ferlito F, et al.Synovial expression of osteopontin correlates with angiogenesis in juvenile idiopathic arthritis[J].Rheumatology( Oxford) , 2004;43:1091-1096.
28 Marciano R, Giacopelli F, Divizia MT, et al.A polymorphic variant inside the osteopontin gene shows association with disease course in oligoarticular juvenile idiopathic arthritis[J].Ann Rheum Dis, 2006;65:662-665.

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