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Erschienen in: Rheumatology International 6/2016

04.03.2016 | Genes and Disease

Unique gene expression profile in osteoarthritis synovium compared with cartilage: analysis of publicly accessible microarray datasets

verfasst von: Robin Park, Jong Dae Ji

Erschienen in: Rheumatology International | Ausgabe 6/2016

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Abstract

The purpose of this study was to identify a gene expression signature in osteoarthritis (OA) synovium and genomic pathways likely to be involved in the pathogenesis of OA. Four publicly accessible microarray studies from synovium of OA patients were integrated, and a transcriptomic and network-based meta-analysis was performed. Based on pathways according to the Kyoto Encyclopedia of Genes and Genomes, functional enrichment analysis was performed. Meta-analysis results of OA synovium were compared to two previously published studies of OA cartilage to determine the relative number of common and specific DEGs of the cartilage and synovium. According to our meta-analysis, a total of 1350 genes were found to be differentially expressed in the synovium of OA patients as compared to that of healthy controls. Pathway analysis found 41 significant pathways in the total DEGs, and 22 and 16 pathways in the upregulated and downregulated DEGs, respectively. Cell adhesion molecules and cytokine–cytokine receptor interaction were the most significant pathway in the upregulated and downregulated DEGs, respectively. Comparison of meta-analysis results of OA synovium with results of two previous studies of OA cartilage identified 85 common genes and 1632 cartilage-specific DEGs and 1265 synovium-specific DEGs in the first study; and 142 common genes, and 856 cartilage-specific DEGs and 1208 synovium-specific DEGs in the second study. Our results show a small overlap between the DEGs of the synovium compared to DEGs of the cartilage, suggesting different pathogenic mechanisms that are specific to the synovium.
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Literatur
10.
Zurück zum Zitat Attur M, Belitskaya-Levy I, Oh C, Krasnokutsky S, Greenberg J, Samuels J, Smiles S, Lee S, Patel J, Al-Mussawir H, McDaniel G, Kraus VB, Abramson SB (2011) Increased interleukin-1beta gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum 63(7):1908–1917. doi:10.1002/art.30360 CrossRefPubMedPubMedCentral Attur M, Belitskaya-Levy I, Oh C, Krasnokutsky S, Greenberg J, Samuels J, Smiles S, Lee S, Patel J, Al-Mussawir H, McDaniel G, Kraus VB, Abramson SB (2011) Increased interleukin-1beta gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum 63(7):1908–1917. doi:10.​1002/​art.​30360 CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Geyer M, Grassel S, Straub RH, Schett G, Dinser R, Grifka J, Gay S, Neumann E, Muller-Ladner U (2009) Differential transcriptome analysis of intraarticular lesional vs intact cartilage reveals new candidate genes in osteoarthritis pathophysiology. Osteoarthritis Cartilage 17(3):328–335. doi:10.1016/j.joca.2008.07.010 CrossRefPubMed Geyer M, Grassel S, Straub RH, Schett G, Dinser R, Grifka J, Gay S, Neumann E, Muller-Ladner U (2009) Differential transcriptome analysis of intraarticular lesional vs intact cartilage reveals new candidate genes in osteoarthritis pathophysiology. Osteoarthritis Cartilage 17(3):328–335. doi:10.​1016/​j.​joca.​2008.​07.​010 CrossRefPubMed
12.
13.
14.
15.
Zurück zum Zitat Ramos YF, den Hollander W, Bovee JV, Bomer N, van der Breggen R, Lakenberg N, Keurentjes JC, Goeman JJ, Slagboom PE, Nelissen RG, Bos SD, Meulenbelt I (2014) Genes involved in the osteoarthritis process identified through genome wide expression analysis in articular cartilage; the RAAK study. PLoS One 9(7):e103056. doi:10.1371/journal.pone.0103056 CrossRefPubMedPubMedCentral Ramos YF, den Hollander W, Bovee JV, Bomer N, van der Breggen R, Lakenberg N, Keurentjes JC, Goeman JJ, Slagboom PE, Nelissen RG, Bos SD, Meulenbelt I (2014) Genes involved in the osteoarthritis process identified through genome wide expression analysis in articular cartilage; the RAAK study. PLoS One 9(7):e103056. doi:10.​1371/​journal.​pone.​0103056 CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Woetzel D, Huber R, Kupfer P, Pohlers D, Pfaff M, Driesch D, Haupl T, Koczan D, Stiehl P, Guthke R, Kinne RW (2014) Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation. Arthritis Res. Ther 16(2):R84. doi:10.1186/ar4526 CrossRefPubMedPubMedCentral Woetzel D, Huber R, Kupfer P, Pohlers D, Pfaff M, Driesch D, Haupl T, Koczan D, Stiehl P, Guthke R, Kinne RW (2014) Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation. Arthritis Res. Ther 16(2):R84. doi:10.​1186/​ar4526 CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Xu Y, Barter MJ, Swan DC, Rankin KS, Rowan AD, Santibanez-Koref M, Loughlin J, Young DA (2012) Identification of the pathogenic pathways in osteoarthritic hip cartilage: commonality and discord between hip and knee OA. Osteoarthritis Cartilage 20(9):1029–1038. doi:10.1016/j.joca.2012.05.006 CrossRefPubMed Xu Y, Barter MJ, Swan DC, Rankin KS, Rowan AD, Santibanez-Koref M, Loughlin J, Young DA (2012) Identification of the pathogenic pathways in osteoarthritic hip cartilage: commonality and discord between hip and knee OA. Osteoarthritis Cartilage 20(9):1029–1038. doi:10.​1016/​j.​joca.​2012.​05.​006 CrossRefPubMed
18.
Zurück zum Zitat Wang Q, Rozelle AL, Lepus CM, Scanzello CR, Song JJ, Larsen DM, Crish JF, Bebek G, Ritter SY, Lindstrom TM, Hwang I, Wong HH, Punzi L, Encarnacion A, Shamloo M, Goodman SB, Wyss-Coray T, Goldring SR, Banda NK, Thurman JM, Gobezie R, Crow MK, Holers VM, Lee DM, Robinson WH (2011) Identification of a central role for complement in osteoarthritis. Nat Med 17(12):1674–1679. doi:10.1038/nm.2543 CrossRefPubMedPubMedCentral Wang Q, Rozelle AL, Lepus CM, Scanzello CR, Song JJ, Larsen DM, Crish JF, Bebek G, Ritter SY, Lindstrom TM, Hwang I, Wong HH, Punzi L, Encarnacion A, Shamloo M, Goodman SB, Wyss-Coray T, Goldring SR, Banda NK, Thurman JM, Gobezie R, Crow MK, Holers VM, Lee DM, Robinson WH (2011) Identification of a central role for complement in osteoarthritis. Nat Med 17(12):1674–1679. doi:10.​1038/​nm.​2543 CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Aigner T, Fundel K, Saas J, Gebhard PM, Haag J, Weiss T, Zien A, Obermayr F, Zimmer R, Bartnik E, Bartnik E (2006) Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. Arthritis Rheum 54(11):3533–3544. doi:10.1002/art.22174 CrossRefPubMed Aigner T, Fundel K, Saas J, Gebhard PM, Haag J, Weiss T, Zien A, Obermayr F, Zimmer R, Bartnik E, Bartnik E (2006) Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. Arthritis Rheum 54(11):3533–3544. doi:10.​1002/​art.​22174 CrossRefPubMed
23.
Zurück zum Zitat Breuer K, Foroushani AK, Laird MR, Chen C, Sribnaia A, Lo R, Winsor GL, Hancock RE, Brinkman FS, Lynn DJ (2013) InnateDB: systems biology of innate immunity and beyond–recent updates and continuing curation. Nucleic Acids Res 41(Database issue):D1228–D1233. doi:10.1093/nar/gks1147 CrossRefPubMedPubMedCentral Breuer K, Foroushani AK, Laird MR, Chen C, Sribnaia A, Lo R, Winsor GL, Hancock RE, Brinkman FS, Lynn DJ (2013) InnateDB: systems biology of innate immunity and beyond–recent updates and continuing curation. Nucleic Acids Res 41(Database issue):D1228–D1233. doi:10.​1093/​nar/​gks1147 CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Ungethuem U, Haeupl T, Witt H, Koczan D, Krenn V, Huber H, von Helversen TM, Drungowski M, Seyfert C, Zacher J, Pruss A, Neidel J, Lehrach H, Thiesen HJ, Ruiz P, Blass S (2010) Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis. Physiol Genom 42A(4):267–282. doi:10.1152/physiolgenomics.00004.2010 CrossRef Ungethuem U, Haeupl T, Witt H, Koczan D, Krenn V, Huber H, von Helversen TM, Drungowski M, Seyfert C, Zacher J, Pruss A, Neidel J, Lehrach H, Thiesen HJ, Ruiz P, Blass S (2010) Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis. Physiol Genom 42A(4):267–282. doi:10.​1152/​physiolgenomics.​00004.​2010 CrossRef
25.
Zurück zum Zitat Morales-Ducret J, Wayner E, Elices MJ, Alvaro-Gracia JM, Zvaifler NJ, Firestein GS (1992) Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes. J Immunol 149(4):1424–1431PubMed Morales-Ducret J, Wayner E, Elices MJ, Alvaro-Gracia JM, Zvaifler NJ, Firestein GS (1992) Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes. J Immunol 149(4):1424–1431PubMed
26.
Zurück zum Zitat Pulsatelli L, Assirelli E, Dolzani P, Addimanda O, Mancarella L, Pavloska B, Facchini A, Meliconi R (2013) Increased serum vascular cell adhesion molecule (VCAM)-1 levels in patients with erosive hand osteoarthritis. Rheumatology 52(2):400–402. doi:10.1093/rheumatology/kes309 CrossRefPubMed Pulsatelli L, Assirelli E, Dolzani P, Addimanda O, Mancarella L, Pavloska B, Facchini A, Meliconi R (2013) Increased serum vascular cell adhesion molecule (VCAM)-1 levels in patients with erosive hand osteoarthritis. Rheumatology 52(2):400–402. doi:10.​1093/​rheumatology/​kes309 CrossRefPubMed
27.
Zurück zum Zitat Schett G, Kiechl S, Bonora E, Zwerina J, Mayr A, Axmann R, Weger S, Oberhollenzer F, Lorenzini R, Willeit J (2009) Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints. Arthritis Rheum 60(8):2381–2389. doi:10.1002/art.24757 CrossRefPubMed Schett G, Kiechl S, Bonora E, Zwerina J, Mayr A, Axmann R, Weger S, Oberhollenzer F, Lorenzini R, Willeit J (2009) Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints. Arthritis Rheum 60(8):2381–2389. doi:10.​1002/​art.​24757 CrossRefPubMed
29.
Zurück zum Zitat Tsuchida AI, Beekhuizen M, ’t Hart MC, Radstake TR, Dhert WJ, Saris DB, van Osch GJ, Creemers LB (2014) Cytokine profiles in the joint depend on pathology, but are different between synovial fluid, cartilage tissue and cultured chondrocytes. Arthritis Res Ther 16(5):441. doi:10.1186/s13075-014-0441-0 CrossRefPubMedPubMedCentral Tsuchida AI, Beekhuizen M, ’t Hart MC, Radstake TR, Dhert WJ, Saris DB, van Osch GJ, Creemers LB (2014) Cytokine profiles in the joint depend on pathology, but are different between synovial fluid, cartilage tissue and cultured chondrocytes. Arthritis Res Ther 16(5):441. doi:10.​1186/​s13075-014-0441-0 CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Moller B, Kukoc-Zivojnov N, Kessler U, Rehart S, Kaltwasser JP, Hoelzer D, Kalina U, Ottmann OG (2001) Expression of interleukin-18 and its monokine-directed function in rheumatoid arthritis. Rheumatology 40(3):302–309CrossRefPubMed Moller B, Kukoc-Zivojnov N, Kessler U, Rehart S, Kaltwasser JP, Hoelzer D, Kalina U, Ottmann OG (2001) Expression of interleukin-18 and its monokine-directed function in rheumatoid arthritis. Rheumatology 40(3):302–309CrossRefPubMed
31.
32.
Zurück zum Zitat Gracie JA, Forsey RJ, Chan WL, Gilmour A, Leung BP, Greer MR, Kennedy K, Carter R, Wei XQ, Xu D, Field M, Foulis A, Liew FY, McInnes IB (1999) A proinflammatory role for IL-18 in rheumatoid arthritis. J Clin Investig 104(10):1393–1401. doi:10.1172/JCI7317 CrossRefPubMedPubMedCentral Gracie JA, Forsey RJ, Chan WL, Gilmour A, Leung BP, Greer MR, Kennedy K, Carter R, Wei XQ, Xu D, Field M, Foulis A, Liew FY, McInnes IB (1999) A proinflammatory role for IL-18 in rheumatoid arthritis. J Clin Investig 104(10):1393–1401. doi:10.​1172/​JCI7317 CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Park CC, Morel JC, Amin MA, Connors MA, Harlow LA, Koch AE (2001) Evidence of IL-18 as a novel angiogenic mediator. J Immunol 167(3):1644–1653CrossRefPubMed Park CC, Morel JC, Amin MA, Connors MA, Harlow LA, Koch AE (2001) Evidence of IL-18 as a novel angiogenic mediator. J Immunol 167(3):1644–1653CrossRefPubMed
35.
Zurück zum Zitat Olee T, Hashimoto S, Quach J, Lotz M (1999) IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses. J Immunol 162(2):1096–1100PubMed Olee T, Hashimoto S, Quach J, Lotz M (1999) IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses. J Immunol 162(2):1096–1100PubMed
36.
Zurück zum Zitat Wang Y, Xu D, Long L, Deng X, Tao R, Huang G (2014) Correlation between plasma, synovial fluid and articular cartilage Interleukin-18 with radiographic severity in 33 patients with osteoarthritis of the knee. Clin Exp Med 14(3):297–304. doi:10.1007/s10238-013-0251-8 CrossRefPubMed Wang Y, Xu D, Long L, Deng X, Tao R, Huang G (2014) Correlation between plasma, synovial fluid and articular cartilage Interleukin-18 with radiographic severity in 33 patients with osteoarthritis of the knee. Clin Exp Med 14(3):297–304. doi:10.​1007/​s10238-013-0251-8 CrossRefPubMed
37.
Zurück zum Zitat Szekanecz Z, Vegvari A, Szabo Z, Koch AE (2010) Chemokines and chemokine receptors in arthritis. Front Biosci 2:153–167CrossRef Szekanecz Z, Vegvari A, Szabo Z, Koch AE (2010) Chemokines and chemokine receptors in arthritis. Front Biosci 2:153–167CrossRef
40.
Zurück zum Zitat Blom AB, Brockbank SM, van Lent PL, van Beuningen HM, Geurts J, Takahashi N, van der Kraan PM, van de Loo FA, Schreurs BW, Clements K, Newham P, van den Berg WB (2009) Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum 60(2):501–512. doi:10.1002/art.24247 CrossRefPubMed Blom AB, Brockbank SM, van Lent PL, van Beuningen HM, Geurts J, Takahashi N, van der Kraan PM, van de Loo FA, Schreurs BW, Clements K, Newham P, van den Berg WB (2009) Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum 60(2):501–512. doi:10.​1002/​art.​24247 CrossRefPubMed
41.
Zurück zum Zitat Baker N, Sharpe P, Culley K, Otero M, Bevan D, Newham P, Barker W, Clements KM, Langham CJ, Goldring MB, Gavrilovic J (2012) Dual regulation of metalloproteinase expression in chondrocytes by Wnt-1-inducible signaling pathway protein 3/CCN6. Arthritis Rheum 64(7):2289–2299. doi:10.1002/art.34411 CrossRefPubMedPubMedCentral Baker N, Sharpe P, Culley K, Otero M, Bevan D, Newham P, Barker W, Clements KM, Langham CJ, Goldring MB, Gavrilovic J (2012) Dual regulation of metalloproteinase expression in chondrocytes by Wnt-1-inducible signaling pathway protein 3/CCN6. Arthritis Rheum 64(7):2289–2299. doi:10.​1002/​art.​34411 CrossRefPubMedPubMedCentral
42.
Zurück zum Zitat Ramos YF, Bos SD, van der Breggen R, Kloppenburg M, Ye K, Lameijer EW, Nelissen RG, Slagboom PE, Meulenbelt I (2015) A gain of function mutation in TNFRSF11B encoding osteoprotegerin causes osteoarthritis with chondrocalcinosis. Ann Rheum Dis 74(9):1756–1762. doi:10.1136/annrheumdis-2013-205149 CrossRefPubMed Ramos YF, Bos SD, van der Breggen R, Kloppenburg M, Ye K, Lameijer EW, Nelissen RG, Slagboom PE, Meulenbelt I (2015) A gain of function mutation in TNFRSF11B encoding osteoprotegerin causes osteoarthritis with chondrocalcinosis. Ann Rheum Dis 74(9):1756–1762. doi:10.​1136/​annrheumdis-2013-205149 CrossRefPubMed
43.
Zurück zum Zitat Litherland GJ, Dixon C, Lakey RL, Robson T, Jones D, Young DA, Cawston TE, Rowan AD (2008) Synergistic collagenase expression and cartilage collagenolysis are phosphatidylinositol 3-kinase/Akt signaling-dependent. J Biol Chem 283(21):14221–14229. doi:10.1074/jbc.M710136200 CrossRefPubMed Litherland GJ, Dixon C, Lakey RL, Robson T, Jones D, Young DA, Cawston TE, Rowan AD (2008) Synergistic collagenase expression and cartilage collagenolysis are phosphatidylinositol 3-kinase/Akt signaling-dependent. J Biol Chem 283(21):14221–14229. doi:10.​1074/​jbc.​M710136200 CrossRefPubMed
Metadaten
Titel
Unique gene expression profile in osteoarthritis synovium compared with cartilage: analysis of publicly accessible microarray datasets
verfasst von
Robin Park
Jong Dae Ji
Publikationsdatum
04.03.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Rheumatology International / Ausgabe 6/2016
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-016-3451-1

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