Immunopathogenesis of osteoarthritis

Clinical Immunology

Volumn 146, Issue 3, 2013, Pages 185-196

  Haseeb, Abdul ^a   Haqqi, Tariq M ^a  

^a Northeastern Ohio Medical University   (United States)

Author keywords

B cells; Chemokines; Complement system; Cytokines; Osteoarthritis; T cells

Indexed keywords

ADALIMUMAB; AUTOANTIGEN; CHEMOKINE; CYTOKINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLIXIMAB; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 6; MATRIX METALLOPROTEINASE; MYELOID DIFFERENTIATION FACTOR 88; ONCOSTATIN M; PROSTAGLANDIN E2; RECOMBINANT INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA;

ADAPTIVE IMMUNITY; ARTICULAR CARTILAGE; B LYMPHOCYTE; CELL INFILTRATION; CELLULAR IMMUNITY; COMPLEMENT ACTIVATION; COMPLEMENT SYSTEM; CYTOKINE RELEASE; GENE THERAPY; HEREDITY; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOPATHOGENESIS; INNATE IMMUNITY; MACROPHAGE; MONOCYTE; NONHUMAN; OSTEOARTHRITIS; PRIORITY JOURNAL; PROSTAGLANDIN RELEASE; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; SYNOVIUM; T LYMPHOCYTE; TISSUE INJURY;

ADAPTIVE IMMUNITY; ANIMALS; HUMANS; IMMUNITY, INNATE; OSTEOARTHRITIS; SIGNAL TRANSDUCTION;

EID: 84872864942     PISSN: 15216616     EISSN: 15217035     Source Type: Journal    
DOI: 10.1016/j.clim.2012.12.011     Document Type: Review

References (177)

1. Creamer P., Hochberg M.C. Osteoarthritis. Lancet 1997, 350:503-508.
2. Brandt K.D., Dieppe P., Radin E. Etiopathogenesis of osteoarthritis. Med. Clin. North Am. 2009, 93:1-24.
3. Lane Smith R., Trindade M.C., Ikenoue T., et al. Effects of shear stress on articular chondrocyte metabolism. Biorheology 2000, 37:95-107.
4. Jasin H.E. Immune mediated cartilage destruction. Scand. J. Rheumatol. Suppl. 1988, 76:111-116.
5. Ayral X., Pickering E.H., Woodworth T.G., et al. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis-results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthr. Cartil. 2005, 13:361-367.
6. Hill C.L., Hunter D.J., Niu J., et al. Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann. Rheum. Dis. 2007, 66:1599-1603.
7. Revell P.A., Mayston V., Lalor P., Mapp P. The synovial membrane in osteoarthritis: a histological study including the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies. Ann. Rheum. Dis. 1988, 47:300-307.
8. Sakkas L.I., Scanzello C., Johanson N., et al. T cells and T-cell cytokine transcripts in the synovial membrane in patients with osteoarthritis. Clin. Diagn. Lab. Immunol. 1998, 5:430-437.
9. Nakamura H., Yoshino S., Kato T., et al. T-cell mediated inflammatory pathway in osteoarthritis. Osteoarthr. Cartil. 1999, 7:401-402.
10. Wang Q., Rozelle A.L., Lepus C.M., et al. Identification of a central role for complement in osteoarthritis. Nat. Med. 2011, 17:1674-1679.
11. Walsh D.A., Bonnet C.S., Turner E.L., et al. Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis. Osteoarthr. Cartil. 2007, 15:743-751.
12. Benito M.J., Veale D.J., FitzGerald O., et al. Synovial tissue inflammation in early and late osteoarthritis. Ann. Rheum. Dis. 2005, 64:1263-1267.
13. Van Lent P.L., Blom A.B., van der Kraan P., et al. Crucial role of synovial lining macrophages in the promotion of transforming growth factor β-mediated osteophyte formation. Arthritis Rheum. 2004, 50:103-111.
14. Blom A.B., van Lent P.L., Libregts S., et al. Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3. Arthritis Rheum. 2007, 56:147-157.
15. Bondeson J., Wainwright S.D., Lauder S., et al. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res. Ther. 2006, 8:R187.
16. Huss R.S., Huddleston J.I., Goodman S.B., et al. Synovial tissue-infiltrating natural killer cells in osteoarthritis and periprosthetic inflammation. Arthritis Rheum. 2010, 62:3799-3805.
17. Pettit A.R., Ahern M.J., Zehntner S., et al. Comparison of differentiated dendritic cell infiltration of autoimmune and osteoarthritis synovial tissue. Arthritis Rheum. 2001, 44:105-110.
18. Cao Y., Meng H., et al. Dendritic cells of synovium in experimental model of osteoarthritis of rabbits. Cell. Physiol. Biochem. 2012, 30:23-32.
19. Gabay R., Micheli A., Fallet G.H. Behaviour of synovial complement C3 and C4 components in inflammatory and degenerative joint diseases, before and after synoviorthesis. Ann. Rheum. Dis. 1975, 34:166-170.
20. Cooke T.D., Bennett E.L., Ohno O. The deposition of immunoglobulins and complement in osteoarthritic cartilage. Int. Orthop. 1980, 4:211-217.
21. Moskowitz R.W., Kresina T.F. Immunofluorescent analysis of experimental osteoarthritic cartilage and synovium: evidence for selective deposition of immunoglobulin and complement in cartilaginous tissues. J. Rheumatol. 1986, 13:391-396.
22. Cantatore F.P., Benazzo F., Ribatti D., et al. Early alteration of synovial membrane in osteoarthrosis. Clin. Rheumatol. 1988, 7:214-219.
23. Tarkowski A., Trollmo C., Seifert P.S., Hansson G.K. Expression of decay-accelerating factor on synovial lining cells in inflammatory and degenerative arthritides. Rheumatol. Int. 1992, 12:201-205.
24. Corvetta A., Pomponio G., Rinaldi N., et al. Terminal complement complex in synovial tissue from patients affected by rheumatoid arthritis, osteoarthritis and acute joint trauma. Clin. Exp. Rheumatol. 1992, 10:433-438.
25. Doherty M., Richards N., Hornby J., Powell R. Relation between synovial fluid C3 degradation products and local joint inflammation in rheumatoid arthritis, osteoarthritis, and crystal associated arthropathy. Ann. Rheum. Dis. 1988, 47:190-197.
26. Ammitzboll C.G., Thiel S., Ellingsen T., et al. Levels of lectin pathway proteins in plasma and synovial fluid of rheumatoid arthritis and osteoarthritis. Rheumatol. Int. 2012, 32:1457-1463.
27. Gobezie R., Kho A., Krastins B., et al. High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis. Arthritis Res. Ther. 2007, 9:R36.
28. Mateos J., Lourido L., Fernández-Puente P., et al. Differential protein profiling of synovial fluid from rheumatoid arthritis and osteoarthritis patients using LC-MALDI TOF/TOF. J. Proteomics 2012, 75:2869-2878.
29. Fernández-Puente P., Mateos J., Fernández-Costa C., et al. Identification of a panel of novel serum osteoarthritis biomarkers. J. Proteome Res. 2011, 10:5095-5101.
30. Rosenthal A.K., Gohr C.M., Ninomiya J., Wakim B.T. Proteomic analysis of articular cartilage vesicles from normal and osteoarthritic cartilage. Arthritis Rheum. 2011, 63:401-411.
31. Geyer M., Grässel S., Straub R.H., et al. Differential transcriptome analysis of intraarticular lesional vs intact cartilage reveals new candidate genes in osteoarthritis pathophysiology. Osteoarthr. Cartil. 2009, 17:328-335.
32. Ruddy S., Colten H.R. Rheumatoid arthritis. Biosynthesis of complement proteins by synovial tissues. N. Engl. J. Med. 1974, 290:1284-1288.
33. Katz Y., Strunk R.C. Synovial fibroblast-like cells synthesize seven proteins of the complement system. Arthritis Rheum. 1988, 31:1365-1370.
34. Firestein G.S., Paine M.M., Littman B.H. Gene expression (collagenase, tissue inhibitor of metalloproteinases, complement, and HLA-DR) in rheumatoid arthritis and osteoarthritis synovium. Quantitative analysis and effect of intraarticular corticosteroids. Arthritis Rheum. 1991, 34:1094-1105.
35. Breitner S., Storkel S., Reichel W., Loos M. Complement components C1q, C1r/C1s, and C1INH in rheumatoid arthritis. Correlation of in situ hybridization and northern blot results with function and protein concentration in synovium and primary cell cultures. Arthritis Rheum. 1995, 38:492-498.
36. Onuma H., Masuko-Hongo K., Yuan G., et al. Expression of the anaphylatoxin receptor C5aR (CD88) by human articular chondrocytes. Rheumatol. Int. 2002, 22:52-55.
37. Clemmons D.R., Busby W.H., Garmong A., et al. Inhibition of insulin-like growth factor binding protein 5 proteolysis in articular cartilage and joint fluid results in enhanced concentrations of insulin-like growth factor 1 and is associated with improved osteoarthritis. Arthritis Rheum. 2002, 46:694-703.
38. Busby W.H., Yocum S.A., Rowland M., et al. Complement 1s is the serine protease that cleaves IGFBP-5 in human osteoarthritic joint fluid. Osteoarthr. Cartil. 2009, 17:547-555.
39. Scanzello C.R., Goldring S.R. The role of synovitis in osteoarthritis pathogenesis. Bone 2012, 51:249-257.
40. Smith M.D., Triantafillou S., Parker A., et al. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J. Rheumatol. 1997, 24:365-371.
41. Kubota E., Imamura H., Kubota T., et al. Interleukin 1 beta and stromelysin (MMP3) activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint. J. Oral Maxillofac. Surg. 1997, 55:20-27.
42. Loeser R.F., Carlson C.S., Del Carlo M., Cole A. Detection of nitrotyrosine in aging and osteoarthritic cartilage: correlation of oxidative damage with the presence of interleukin 1ß and with chondrocyte resistance to insulin-like growth factor 1. Arthritis Rheum. 2002, 46:2349-2357.
43. Pelletier J.P., McCollum R., Cloutier J.M., Martel-Pelletier J. Synthesis of metalloproteases and interleukin 6 (IL-6) in human osteoarthritic synovial membrane is an IL-1 mediated process. J. Rheumatol. 1995, 43:109-114.
44. Shlopov B.V., Gumanovskaya M.L., Hasty K.A. Autocrine regulation of collagenase 3 (matrix metalloproteinase 13) during osteoarthritis. Arthritis Rheum. 2000, 43:195-205.
45. Sadouk M.B., Pelletier J.P., Tardif G., et al. Human synovial fibroblasts coexpress IL-1 receptor type I and type II mRNA. The increased level of the IL-1 receptor in osteoarthritic cells is related to an increased level of the type I receptor. Lab Invest. 1995, 73:347-355.
46. Wheaton A.J., Borthakur A., Dodge G.R., et al. Sodium magnetic resonance imaging of proteoglycan depletion in an in vivo model of osteoarthritis. Acad. Radiol. 2004, 11:21-28.
47. Lai Y.C., Shaftel S.S., Miller J.N., et al. Intraarticular induction of interleukin-1ß expression in the adult mouse, with resultant temporomandibular joint pathologic changes, dysfunction, and pain. Arthritis Rheum. 2006, 54:1184-1197.
48. Tetlow L.C., Adlam D.J., Woolley D.E. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum. 2001, 44:585-594.
49. Inoue K., Masuko-Hongo K., Okamoto M., Nishioka K. Induction of vascular endothelial growth factor and matrix metalloproteinase-3 (stromelysin) by interleukin-1 in human articular chondrocytes and synoviocytes. Rheumatol. Int. 2005, 26:93-98.
50. Kobayashi M., Squires G.R., Mousa A., et al. Role of interleukin-1 and tumor necrosis factor α in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum. 2005, 52:128-135.
51. Fan Z., Bau B., Yang H., et al. Freshly isolated osteoarthritic chondrocytes are catabolically more active than normal chondrocytes, but less responsive to catabolic stimulation with interleukin-1ß. Arthritis Rheum. 2005, 52:136-143.
52. Bondeson J., Lauder S., Wainwright S., et al. Adenoviral gene transfer of the endogenous inhibitor IkappaBalpha into human osteoarthritis synovial fibroblasts demonstrates that several matrix metalloproteinases and aggrecanases are nuclear factor-kappaB-dependent. J. Rheumatol. 2007, 34:523-533.
53. Cortial D., Gouttenoire J., Rousseau C.F., et al. Activation by IL-1 of bovine articular chondrocytes in culture within a 3D collagen-based scaffold. An in vitro model to address the effect of compounds with therapeutic potential in osteoarthritis. Osteoarthr. Cartil. 2006, 14:631-640.
54. Goldring M.B., Birkhead J., Sandell L.J., et al. 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. 1988, 82:2026-2037.
55. Chadjichristos C., Ghayor C., Kypriotou M., et al. Sp1 and Sp3 transcription factors mediate interleukin-1β down-regulation of human type II collagen gene expression in articular chondrocytes. J. Biol. Chem. 2003, 278:39762-39772.
56. Nietfeld J.J., Wilbrink B., Den Otter W., et al. The effect of human interleukin 1 on proteoglycan metabolism in human and porcine cartilage explants. J. Rheumatol. 1990, 17:818-826.
57. Stöve J., Huch K., Günther K.P., Scharf H.P. Interleukin-1β induces different gene expression of stromelysin, aggrecan and tumor-necrosis-factor-stimulated gene 6 in human osteoarthritic chondrocytes in vitro. Pathobiology 2000, 68:144-149.
58. Gouze J.N., Bordji K., Gulberti S., et al. Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1beta-mediated effects in rat chondrocytes. Arthritis Rheum. 2001, 44:351-360.
59. Heraud F., Heraud A., Harmand M.F. Apoptosis in normal and osteoarthritic human articular cartilage. Ann. Rheum. Dis. 2000, 59:959-965.
60. Lopez-Armada M.J., Carames B., Lires-Dean M., et al. Cytokines, tumor necrosis factor-α and interleukin-1ß, differentially regulate apoptosis in osteoarthritis cultured human chondrocytes. Osteoarthr. Cartil. 2006, 14:660-669.
61. Pelletier J.P., Mineau F., Ranger P., et al. The increased synthesis of inducible nitric oxide inhibits IL-1ra synthesis by human articular chondrocytes: possible role in osteoarthritic cartilage degradation. Osteoarthr. Cartil. 1996, 4:77-84.
62. Tenor H., Hedbom E., Hauselmann H.J., et al. Phosphodiesterase isoenzyme families in human osteoarthritis chondrocytes-functional importance of phosphodiesterase 4. Br. J. Pharmacol. 2002, 135:609-618.
63. Afonso V., Champy R., Mitrovic D., et al. Reactive oxygen species and superoxide dismutases: role in joint diseases. Joint Bone Spine 2007, 74:324-329.
64. Mathy-Hartert M., Hogge L., Sanchez C., et al. Interleukin-1β and interleukin-6 disturb the antioxidant enzyme system in bovine chondrocytes: a possible explanation for oxidative stress generation. Osteoarthr. Cartil. 2008, 16:756-763.
65. Scott J.L., Gabrielides C., Davidson R.K., et al. Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease. Ann. Rheum. Dis. 2010, 69:1502-1510.
66. Moos V., Fickert S., Müller B., et al. Immunohistological analysis of cytokine expression in human osteoarthritic and healthy cartilage. J. Rheumatol. 1999, 26:870-879.
67. Melchiorri C., Meliconi R., Frizziero L., et al. Enhanced and coordinated in vivo expression of inflammatory cytokines and nitric oxide synthase by chondrocytes from patients with osteoarthritis. Arthritis Rheum. 1998, 41:2165-2174.
68. Schlaak J.F., Pfers I., Meyer Zum Buschenfelde K.H., Marker-Hermann E. Different cytokine profiles in the synovial fluid of patients with osteoarthritis, rheumatoid arthritis and seronegative spondylarthropathies. Clin. Exp. Rheumatol. 1996, 14:155-162.
69. Alaaeddine N., Olee T., Hashimoto S., et al. Production of the chemokine RANTES by articular chondrocytes and role in cartilage degradation. Arthritis Rheum. 2001, 44:1633-1643.
70. Silvestri T., Pulsatelli L., Dolzani P., et al. In vivo expression of inflammatory cytokine receptors in the joint compartments of patients with arthritis. Rheumatol. Int. 2006, 26:360-368.
71. Saklatvala J. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature 1986, 322:547-549.
72. Lefebvre V., Peeters-Joris C., Vaes G. Modulation by interleukin 1 and tumor necrosis factor α of production of collagenase, tissue inhibitor of metalloproteinases and collagen types in differentiated and dedifferentiated articular chondrocytes. Biochim. Biophys. Acta 1990, 1052:366-378.
73. Reboul P., Pelletier J.P., Tardif G., et al. The new collagenase, collagenase-3, is expressed and synthesized by human chondrocytes but not by synoviocytes. A role in osteoarthritis. J. Clin. Invest. 1996, 97:2011-2019.
74. Patel I.R., Attur M.G., Patel R.N., et al. TNF-a convertase enzyme from human arthritis-affected cartilage: isolation of cDNA by differential display, expression of the active enzyme, and regulation of TNF-a. J. Immunol. 1998, 160:4570-4579.
75. Malemud C.J. Anticytokine therapy for osteoarthritis: evidence to date. Drugs Aging 2010, 27:95-115.
76. Calich A.L., Domiciano D.S., Fuller R. Osteoarthritis: can anti-cytokine therapy play a role in treatment?. Clin. Rheumatol. 2010, 29:451-455.
77. Kapoor M., Martel-Pelletier J., Lajeunesse D., et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat. Rev. Rheumatol. 2011, 7:33-42.
78. Zhong Z., Wen Z., Darnell J.E. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 1994, 264:95-98.
79. Guerne P.A., Zuraw B.L., Vaughan J.H., et al. Synovium as a source of interleukin 6 in vitro. Contribution to local and systemic manifestations of arthritis. J. Clin. Invest. 1989, 83:585-592.
80. Guerne P.A., Carson D.A., Lotz M. IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro. J. Immunol. 1992, 144:499-505.
81. Klatt A.R., Zech D., Kuhn G., et al. Discoidin domain receptor 2 mediates the collagen II-dependent release of interleukin-6 in primary human chondrocytes. J. Pathol. 2009, 218:241-247.
82. Inoue H., Takamori M., Shimoyama Y., et al. Regulation by PGE2 of the production of interleukin-6, macrophage colony stimulating factor, and vascular endothelial growth factor in human synovial fibroblasts. Br. J. Pharmacol. 2002, 136:287-295.
83. Tetlow L.C., Woolley D.E. Histamine and PGE(2) stimulate the production of interleukins-6 and -8 by human articular chondrocytes in vitro. Inflamm. Res. 2006, 55(Suppl. 1):S73-S74.
84. Li X., Ellman M., Muddasani P., et al. Prostaglandin E2 and its cognate EP receptors control human adult articular cartilage homeostasis and are linked to the pathophysiology of osteoarthritis. Arthritis Rheum. 2009, 60:513-523.
85. Wang P., Zhu F., Konstantopoulos K. Prostaglandin E2 induces interleukin-6 expression in human chondrocytes via cAMP/protein kinase A- and phosphatidylinositol 3-kinase-dependent NF-kappaB activation. Am. J. Physiol. Cell Physiol. 2010, 298:C1445-C1456.
86. Livshits G., Zhai G., Hart D.J., et al. Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: the Chingford study. Arthritis Rheum. 2009, 60:2037-2045.
87. Cawston T.E., Curry V.A., Summers C.A., et al. The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint. Arthritis Rheum. 1998, 41:1760-1771.
88. Rowan A.D., Koshy P.J., Shingleton W.D., et al. Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum. 2001, 44:1620-1632.
89. Pore'e B., Kypriotou M., Chadjichristos C., et al. Interleukin-6 (IL-6) and 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, 283:4850-4865.
90. Sallusto F., Mackay C.R., Lanzavecchia A. The role of chemokine receptors in primary, effector, and memory immune responses. Annu. Rev. Immunol. 2000, 18:593-620.
91. Borzi R.M., Mazzetti I., Macor S., et al. Flow cytometric analysis of intracellular chemokines in chondrocytes in vivo: constitutive expression and enhancement in osteoarthritis and rheumatoid arthritis. FEBS Lett. 1999, 455:238-242.
92. Akhtar N., Haqqi T.M. Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes. Arthritis Res. Ther. 2013, 13:R93.
93. Pulsatelli L., Dolzani P., Piacentini A., et al. Chemokine production by human chondrocytes. J. Rheumatol. 1999, 26:1992-2001.
94. Borzì R.M., Mazzetti I., Cattini L. Human chondrocytes express functional chemokine receptors and release matrix-degrading enzymes in response to C-X-C and C-C chemokines. Arthritis Rheum. 2000, 43:1734-1741.
95. Mazzetti I., Magagnoli G., Paoletti S., et al. A role for chemokines in the induction of chondrocyte phenotype modulation. Arthritis Rheum. 2004, 50:112-122.
96. Yuan G.H., Masuko-Hongo K., Sakata M., et al. The role of C-C chemokines and their receptors in osteoarthritis. Arthritis Rheum. 2001, 44:1056-1070.
97. Haringman J.J., Smeets T.J., Reinders-Blankert P., Tak P.P. Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis. Ann. Rheum. Dis. 2006, 65:294-300.
98. Endres M., Andreas K., Kalwitz G., et al. Chemokine profile of synovial fluid from normal, osteoarthritis and rheumatoid arthritis patients: CCL25, CXCL10 and XCL1 recruit human subchondral mesenchymal progenitor cells. Osteoarthr. Cartil. 2010, 18:1458-1466.
99. Appleton C.T., Pitelka V., Henry J., Beier F. Global analyses of gene expression in early experimental osteoarthritis. Arthritis Rheum. 2007, 56:1854-1868.
100. Koch A.E., Kunkel S.L., Shah M.R., et al. Macrophage inflammatory protein-1 beta: a C-C chemokine in osteoarthritis. Clin. Immunol. Immunopathol. 1995, 77:307-314.
101. Shen P.C., Wu C.L., Jou I.M., et al. T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ. Osteoarthr. Cartil. 2011, 19:728-736.
102. Borzi R.M., Mazzetti I., Magagnoli G., et al. Growth-related oncogene alpha induction of apoptosis in osteoarthritis chondrocytes. Arthritis Rheum. 2002, 46:3201-3211.
103. Wei L., Sun X., Kanbe K., et al. Chondrocyte death induced by pathological concentration of chemokine stromal cell-derived factor-1. J. Rheumatol. 2006, 33:1818-1826.
104. Chen H.T., Tsou H.K., Hsu C.J., et al. Stromal cell-derived factor-1/CXCR4 promotes IL-6 production in human synovial fibroblasts. J. Cell. Biochem. 2011, 112:1219-1227.
105. Merz D., Liu R., Johnson K., Terkeltaub R. IL-8/CXCL8 and growth-related oncogene alpha/CXCL1 induce chondrocytes hypertrophic differentiation. J. Immunol. 2003, 171:4406-4415.
106. Chauffier K., Laiguillon M.C., Bougault C., et al. Induction of the chemokine IL-8/Kc by the articular cartilage: possible influence on osteoarthritis. Joint Bone Spine 2012, 79:604-609.
107. Hsu Y.H., Hsieh M.S., Liang Y.C., et al. Production of the chemokine eotaxin-1 in osteoarthritis and its role in cartilage degradation. J. Cell. Biochem. 2004, 93:929-939.
108. Brühl H., Mack M., Niedermeier M., et al. Functional expression of the chemokine receptor CCR7 on fibroblast-like synoviocytes. Rheumatology (Oxford) 2008, 47:1771-1774.
109. Lindblad S., Hedfors E. Arthroscopic and immunohistologic characterization of knee joint synovitis in osteoarthritis. Arthritis Rheum. 1987, 30:1081-1088.
110. Sakkas L.I., Scanzello C., Johanson N., et al. T cells and T-cell cytokine transcripts in the synovial membrane in patients with osteoarthritis. Clin. Diagn. Lab. Immunol. 1988, 5:430-437.
111. Kennedy T.D., Plater-Zyberk C., Partridge T.A., et al. Morphometric comparison of synovium from patients with osteoarthritis and rheumatoid arthritis. J. Clin. Pathol. 1988, 41:847-852.
112. Haraoui B., Pelletier J.P., Cloutier J.M., et al. Synovial membrane histology and immunopathology in rheumatoid arthritis and osteoarthritis: in vivo effects of antirheumatic drugs. Arthritis Rheum. 1991, 34:153-163.
113. Ishii H., Tanaka H., Katoh K., et al. Characterization of infiltrating T cells and Th1/Th2-type cytokines in the synovium of patients with osteoarthritis. Osteoarthr. Cartil. 2002, 10:277-281.
114. Zwillich S.H., Fang Q., Kieber-Emmons T., et al. Vα gene usage in rheumatoid compared with osteoarthritic synovial tissue T cells. DNA Cell Biol. 1994, 13:923-931.
115. Scanzello C.R., Sakkas L.I., Johanson N.A., Platsoucas C.D. Oligoclonal populations of T-cells infiltrate the synovial membrane (SM) of patients with osteoarthritis (OA). Arthritis Rheum. 1999, 42(Suppl. 59):S257.
116. Alsalameh S., Mollenhauer J., Hain N., et al. Cellular immune response toward human articular chondrocytes: T cell reactivities against chondrocyte and fibroblast membranes in destructive joint diseases. Arthritis Rheum. 1990, 33:1477-1486.
117. Sakata M., Masuko-Hongo K., Nakamura H., et al. Osteoarthritic articular chondrocytes stimulate autologous T cell responses in vitro. Clin. Exp. Rheumatol. 2003, 21:704-710.
118. Champion B.R., Poole A.R. Immunity to homologous type III collagen after partial meniscectomy and sham surgery in rabbits. Arthritis Rheum. 1982, 25:274-287.
119. Guerassimov A., Zhang Y., Cartman A., et al. Immune responses to cartilage link protein and the G1 domain of proteoglycan aggrecan in patients with osteoarthritis. Arthritis Rheum. 1999, 42:527-533.
120. de Jong H., Berlo S.E., Hombrink P., et al. Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis. Ann. Rheum. Dis. 2010, 69:255-262.
121. Nakamura H., Tanaka M., Masuko-Hongo K., et al. Enhanced production of MMP-1, MMP-3, MMP-13, and RANTES by interaction of chondrocytes with autologous T cells. Rheumatol. Int. 2006, 26:984-990.
122. Shiokawa S., Matsumoto N., Nishimura J. Clonal analysis of B cells in the osteoarthritis synovium. Ann. Rheum. Dis. 2001, 60:802-805.
123. Mollenhauer J., von den Mark K., Burmester G., et al. Serum antibodies against chondrocyte cell surface proteins in osteoarthritis and rheumatoid arthritis. J. Rheumatol. 1988, 15:1811-1817.
124. Sakata M., Tsuruha J.I., Masuko-Hongo K., et al. Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid arthritis. J. Rheumatol. 2001, 28:1492-1495.
125. Tsuruha J., Masuko-Hongo K., Kato T., et al. Implication of cartilage intermediate layer protein in cartilage destruction in subsets of patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 2001, 44:838-845.
126. Tsuruha J., Masuko-Hongo K., Kato T., et al. Autoimmunity against YKL-39, a human cartilage derived protein, in patients with osteoarthritis. J. Rheumatol. 2002, 29:1459-1466.
127. Xiang Y., Sekine T., Nakamura H., et al. Proteomic surveillance of autoimmunity in osteoarthritis: identification of triosephosphate isomerase as an autoantigen in patients with osteoarthritis. Arthritis Rheum. 2004, 50:1511-1521.
128. Charrière G., Hartmann D.J., Vignon E., et al. Antibodies to types I, II, IX, and XI collagen in the serum of patients with rheumatic diseases. Arthritis Rheum. 1988, 31:325-332.
129. Du H., Masuko-Hongo K., Nakamura H., et al. The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: evidence of a variety of autoimmune processes. Rheumatol. Int. 2005, 26:35-41.
130. Caspi D., Anouk M., Golan I., et al. Synovial fluid levels of anti-cyclic citrullinated peptide antibodies and IgA rheumatoid factor in rheumatoid arthritis, psoriatic arthritis, and osteoarthritis. Arthritis Rheum. 2006, 55:53-56.
131. Karopoulos C., Rowley M.J., Ilic M.Z., Handley C.J. Presence of antibodies to native G1 domain of aggrecan core protein in synovial fluids from patients with various joint diseases. Arthritis Rheum. 1996, 39:1990-1997.
132. Niebauer G.W., Wolf B., Yarmush M., Richardson D.W. Evaluation of immune complexes and collagen type-specific antibodies in sera and synovial fluids of horses with secondary osteoarthritis. Am. J. Vet. Res. 1988, 49:1223-1227.
133. De Rooster H., Cox E., van Bree H. Prevalence and relevance of antibodies to type-I and -II collagen in synovial fluid of dogs with cranial cruciate ligament damage. Am. J. Vet. Res. 2000, 61:1456-1461.
134. Jasin H.E. Autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis. Arthritis Rheum. 1985, 28:241-248.
135. Cooke T.D. Significance of immune complex deposits in osteoarthritic cartilage. J. Rheumatol. 1987, 14:77-79.
136. Takagi T., Jasin H.E. Interactions between anticollagen antibodies and chondrocytes. Arthritis Rheum. 1992, 35:224-230.
137. Scanzello C.R., Plaas A., Crow M.K. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound?. Curr. Opin. Rheumatol. 2008, 20:565-572.
138. Chevalier X., Claudepierre P., Groult N., et al. Presence of ED-A containing fibronectin in human articular cartilage from patients with osteoarthritis and rheumatoid arthritis. J. Rheumatol. 1996, 23:1022-1030.
139. Chevalier X., Groult N., Larget-Piet B., et al. Tenascin distribution in articular cartilage from normal subjects and from patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 1994, 37:1013-1022.
140. Midwood K., Sacre S., Piccinini A.M., et al. Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat. Med. 2009, 15:774-780.
141. Belcher C., Yaqub R., Fawthrop F., et al. Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees. Ann. Rheum. Dis. 1997, 56:299-307.
142. Termeer C., Benedix F., Sleeman J., et al. Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4. J. Exp. Med. 2002, 195:99-111.
143. Scheibner K.A., Lutz M.A., Boodoo S., et al. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J. Immunol. 2006, 177:1272-1281.
144. Poole A.R., Rosenberg L.C., Reiner A., et al. Contents and distributions of the proteoglycans decorin and biglycan in normal and osteoarthritic human articular cartilage. J. Orthop. Res. 1996, 14:681-689.
145. Bock H.C., Michaeli P., Bode C., et al. The small proteoglycans decorin and biglycan in human articular cartilage of late-stage osteoarthritis. Osteoarthr. Cartil. 2001, 9:654-663.
146. Schaefer L., Babelova A., Kiss E., et al. The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J. Clin. Invest. 2005, 115:2223-2233.
147. Radstake T.R., Roelofs M.F., Jenniskens Y.M., et al. Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma. Arthritis Rheum. 2004, 50:3856-3865.
148. Ozawa T., Koyama K., Ando T., et al. Thymic stromal lymphopoietin secretion of synovial fibroblasts is positively and negatively regulated by Toll-like receptors/nuclear factor-kappaB pathway and interferon-gamma/dexamethasone. Mod. Rheumatol. 2007, 17:459-463.
149. Kyburz D., Rethage J., Seibl R., et al. Bacterial peptidoglycans but not CpG oligodeoxynucleotides activate synovial fibroblasts by toll-like receptor signaling. Arthritis Rheum. 2003, 48:642-650.
150. Su S.L., Tsai C.D., Lee C.H., et al. Expression and regulation of Toll-like receptor 2 by IL-1β and fibronectin fragments in human articular chondrocytes. Osteoarthr. Cartil. 2005, 13:879-886.
151. Liu-Bryan R., Pritzker K., Firestein G.S., Terkeltaub R. TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation. J. Immunol. 2005, 174:5016-5023.
152. Kim H.A., Cho M.L., Choi H.Y., et al. The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes. Arthritis Rheum. 2006, 54:2152-2163.
153. Zhang Q., Hui W., Litherland G.J., et al. Differential Toll-like receptor dependent collagenase expression in chondrocytes. Ann. Rheum. Dis. 2008, 67:1633-1641.
154. Kuroki K., Stoker A.M., Sims H.J., Cook J.L. Expression of Toll-like receptors 2 and 4 in stifle joint synovial tissues of dogs with or without osteoarthritis. Am. J. Vet. Res. 2010, 71:750-754.
155. Liu-Bryan R., Terkeltaub R. Chondrocyte innate immune myeloid differentiation factor 88-dependent signaling drives procatabolic effects of the endogenous Toll-like receptor 2/Toll-like receptor 4 ligands low molecular weight hyaluronan and high mobility group box chromosomal protein 1 in mice. Arthritis Rheum. 2010, 62:2004-2012.
156. Schelbergen R.F., Blom A.B., van den Bosch M.H., et al. Alarmins S100A8 and S100A9 elicit a catabolic effect in human osteoarthritic chondrocytes that is dependent on Toll-like receptor 4. Arthritis Rheum. 2012, 64:1477-1487.
157. Sohn D.H., Sokolove J., Sharpe O., et al. Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4. Arthritis Res. Ther. 2012, 14:R7.
158. Nair A., Kanda V., Bush-Joseph C., et al. Synovial fluid from patients with early osteoarthritis modulates fibroblast-like synoviocyte responses to toll-like receptor 4 and toll-like receptor 2 ligands via soluble CD14. Arthritis Rheum. 2012, 64:2268-2277.
159. Marcu K.B., Otero M., Olivotto E., et al. NF-kappaB signaling: multiple angles to target OA. Curr. Drug Targets 2010, 11:599-613.
160. Amos N., Lauder S., Evans A., et al. Adenoviral gene transfer into osteoarthritis synovial cells using the endogenous inhibitor IkappaBalpha reveals that most, but not all, inflammatory and destructive mediators are NFkappaB dependent. Rheumatology (Oxford) 2006, 45:1201-1209.
161. Chen L.X., Lin L., Wang H.J., et al. Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-kappaBp65-specific siRNA. Osteoarthr. Cartil. 2008, 16:174-184.
162. Roman-Blas J.A., Jimenez S.A. NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthr. Cartil. 2006, 14:839-848.
163. Khalifé S., Zafarullah M. Molecular targets of natural health products in arthritis. Arthritis Res. Ther. 2011, 13:102.
164. Bremner P., Heinrich M. Natural products as targeted modulators of the nuclear factor-kappaB pathway. J. Pharm. Pharmacol. 2002, 54:453-472.
165. Rasheed Z., Akhtar N., Haqqi T.M. Pomegranate extract inhibits the interleukin-1beta-induced activation of MKK-3, p38alpha-MAPK and transcription factor RUNX-2 in human osteoarthritis chondrocytes. Arthritis Res. Ther. 2010, 12:R195.
166. Pelletier J.P., Caron J.P., Evans C., et al. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum. 1997, 40:1012-1019.
167. Fernandes J.C., Tardif G., Martel-Pelletier J., et al. In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritic rabbit knee joints: prevention of osteoarthritic progression. Am. J. Pathol. 1999, 154:1535-1544.
168. Frisbie D.D., Ghivizzani S.C., Robbins P.D., Evans C.H., McIlwraith C.W. Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene. Gene Ther. 2002, 9:12-20.
169. Zhang X., Mao Z., Yu C. Suppression of early experimental osteoarthritis by gene transfer of interleukin-1 receptor antagonist and interleukin-10. J. Orthop. Res. 2004, 22:742-750.
170. Caron J.P., Fernandes J.C., Martel-Pelletier J., et al. Chondroprotective effect of intra-articular injections of interleukin-1 receptor antagonist in experimental osteoarthritis. Suppression of collagenase-1 expression. Arthritis Rheum. 1996, 39:1535-1544.
171. Chevalier X., Girardeau B., Conrozier T., et al. Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study. J. Rheumatol. 2005, 32:1317-1323.
172. Chevalier X., Goupille P., Beaulieu A.D., et al. Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2009, 61:344-352.
173. Bacconnier L., Jorgensen C., Fabre S. Erosive osteoarthritis of the hand: clinical experience with anakinra. Ann. Rheum. Dis. 2009, 68:1078-1079.
174. Grunke M., Schulze-Koops H. Successful treatment of inflammatory knee osteoarthritis with tumor necrosis factor blockade. Ann. Rheum. Dis. 2006, 65:555-556.
175. Magnano M.D., Chakravarty E.F., Broudy C., et al. A pilot study of tumor necrosis factor inhibition in erosive/inflammatory osteoarthritis of the hands. J. Rheumatol. 2007, 34:1323-1327.
176. Fioravanti A., Fabbroni M., Cerase A., Galeazzi M. Treatment of erosive osteoarthritis of the hands by intra-articular infliximab injections: a pilot study. Rheumatol. Int. 2009, 29:961-965.
177. Hashimoto H., Tomita T., Kunugiza Y., et al. NF-kB decoy oligodeoxynucleotides suppressed the progression of osteoarthritis in rat arthritis. Arthritis Rheum. 2003, 48:S630.