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4. HOXA5 is a key regulator of class 3 semaphorins expression in the synovium of rheumatoid arthritis patients

Author

Martínez-Ramos, Sara, primary, Rafael-Vidal, Carlos, additional, Malvar-Fernández, Beatriz, additional, Rodriguez-Trillo, Angela, additional, Veale, Douglas, additional, Fearon, Ursula, additional, Conde, Carmen, additional, Conde-Aranda, Javier, additional, Radstake, Timothy R D J, additional, Pego-Reigosa, Jose María, additional, Reedquist, Kris A, additional, and García, Samuel, additional

Published
2022
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6. HOXA5 is a key regulator of class 3 semaphorins expression in the synovium of rheumatoid arthritis patients.

Author

Martínez-Ramos, Sara, Rafael-Vidal, Carlos, Malvar-Fernández, Beatriz, Rodriguez-Trillo, Angela, Veale, Douglas, Fearon, Ursula, Conde, Carmen, Conde-Aranda, Javier, Radstake, Timothy R D J, Pego-Reigosa, Jose María, Reedquist, Kris A, and García, Samuel

Subjects
PROTEIN metabolism, ENDOTHELIAL cells, SYNOVIAL membranes, FIBROBLASTS, IMMUNOBLOTTING, CELL survival, CELL motility, COMPARATIVE studies, RHEUMATOID arthritis, MESSENGER RNA, RESEARCH funding, ENZYME-linked immunosorbent assay, TUMOR necrosis factors, TRANSCRIPTION factors
Abstract

Objective Class 3 semaphorins are reduced in the synovial tissue of RA patients and these proteins are involved in the pathogenesis of the disease. The aim of this study was to identify the transcription factors involved in the expression of class 3 semaphorins in the synovium of RA patients. Methods Protein and mRNA expression in synovial tissue from RA and individuals at risk (IAR) patients, human umbilical vein endothelial cells (HUVEC) and RA fibroblast-like synoviocytes (FLS) was determined by ELISA, immunoblotting and quantitative PCR. TCF-3, EBF-1 and HOXA5 expression was knocked down using siRNA. Cell viability, migration and invasion were determined using MTT, calcein, wound closure and invasion assays, respectively. Results mRNA expression of all class 3 semaphorins was significantly lower in the synovium of RA compared with IAR patients. In silico analysis suggested TCF-3, EBF-1 and HOXA5 as transcription factors involved in the expression of these semaphorins. TCF-3, EBF-1 and HOXA5 silencing significantly reduced the expression of several class 3 semaphorin members in FLS and HUVEC. Importantly, HOXA5 expression was significantly reduced in the synovium of RA compared with IAR patients and was negatively correlated with clinical disease parameters. Additionally, TNF-α down-regulated the HOXA5 expression in FLS and HUVEC. Finally, HOXA5 silencing enhanced the migratory and invasive capacities of FLS and the viability of HUVEC. Conclusion HOXA5 expression is reduced during the progression of RA and could be a novel therapeutic strategy for modulating the hyperplasia of the synovium, through the regulation of class 3 semaphorins expression. [ABSTRACT FROM AUTHOR]

Published
2023
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8. Central Role of Semaphorin 3B in a Serum-Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis

Author

Igea, Ana, Carvalheiro, Tiago, Malvar-Fernández, Beatriz, Martinez-Ramos, Sara, Rafael-Vidal, Carlos, Niemantsverdriet, Ellis, Varadé, Jezabel, Fernández-Carrera, Andrea, Jimenez, Norman, McGarry, Trudy, Rodriguez-Trillo, Angela, Veale, Douglas, Fearon, Ursula, Conde, Carmen, Pego-Reigosa, Jose M., González-Fernández, África, Reedquist, Kris A., Radstake, Timothy R.D.J., van der Helm-Van Mil, Annette, García, Samuel, Igea, Ana, Carvalheiro, Tiago, Malvar-Fernández, Beatriz, Martinez-Ramos, Sara, Rafael-Vidal, Carlos, Niemantsverdriet, Ellis, Varadé, Jezabel, Fernández-Carrera, Andrea, Jimenez, Norman, McGarry, Trudy, Rodriguez-Trillo, Angela, Veale, Douglas, Fearon, Ursula, Conde, Carmen, Pego-Reigosa, Jose M., González-Fernández, África, Reedquist, Kris A., Radstake, Timothy R.D.J., van der Helm-Van Mil, Annette, and García, Samuel

Abstract

Objective: Semaphorin 3B (Sema3B) decreases the migratory and invasive capacities of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) and suppresses expression of matrix metalloproteinases. We undertook this study to examine the role of Sema3B in a mouse model of arthritis and its expression in RA patients. Methods: Clinical responses, histologic features, and FLS function were examined in wild-type (WT) and Sema3B−/− mice in a K/BxN serum transfer model of arthritis. Protein and messenger RNA expression of Sema3B in mouse joints and murine FLS, as well as in serum and synovial tissue from patients with arthralgia and patients with RA, was determined using enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, and RNA sequencing. FLS migration was determined using a wound closure assay. Results: The clinical severity of serum-induced arthritis was significantly higher in Sema3B−/− mice compared to WT mice. This was associated with increased expression of inflammatory mediators and increased migratory capacity of murine FLS. Administration of recombinant mouse Sema3B reduced the clinical severity of serum-induced arthritis and the expression of inflammatory mediators. Sema3B expression was significantly lower in the synovial tissue and serum of patients with established RA compared to patients with arthralgia. Serum Sema3B levels were elevated in patients with arthralgia that later progressed to RA, but not in those who did not develop RA; however, these levels drastically decreased 1 and 2 years after RA development. Conclusion: Sema3B expression plays a protective role in a mouse model of arthritis. In RA patients, expression levels of Sema3B in the serum depend on the disease stage, suggesting different regulatory roles in disease onset and progression.

Published
2022

9. Association of MicroRNA‐618 Expression With Altered Frequency and Activation of Plasmacytoid Dendritic Cells in Patients With Systemic Sclerosis

Author

Rossato, Marzia, Affandi, Alsya J., Thordardottir, Soley, Wichers, Catharina G. K., Cossu, Marta, Broen, Jasper C. A., Moret, Frederique M., Bossini‐Castillo, Lara, Chouri, Eleni, van Bon, Lenny, Wolters, Femke, Marut, Wioleta, van der Kroef, Maarten, Silva‐Cardoso, Sandra, Bekker, Cornelis P. J., Dolstra, Harry, van Laar, Jacob M., Martin, Javier, van Roon, Joel A. G., Reedquist, Kris A., Beretta, Lorenzo, and Radstake, Timothy R. D. J.

Published
2017
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12. Central Role of Semaphorin 3B in a Serum‐Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis

Author

Igea, Ana, primary, Carvalheiro, Tiago, additional, Malvar‐Fernández, Beatriz, additional, Martinez‐Ramos, Sara, additional, Rafael‐Vidal, Carlos, additional, Niemantsverdriet, Ellis, additional, Varadé, Jezabel, additional, Fernández‐Carrera, Andrea, additional, Jimenez, Norman, additional, McGarry, Trudy, additional, Rodriguez‐Trillo, Angela, additional, Veale, Douglas, additional, Fearon, Ursula, additional, Conde, Carmen, additional, Pego‐Reigosa, Jose M., additional, González‐Fernández, África, additional, Reedquist, Kris A., additional, Radstake, Timothy R. D. J., additional, van der Helm‐Van Mil, Annette, additional, and García, Samuel, additional

Published
2022
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15. Hypoxia and TLR9 activation drive CXCL4 production in systemic sclerosis plasmacytoid dendritic cells via mtROS and HIF-2α

Author

Ottria, Andrea, primary, Zimmermann, Maili, additional, Paardekooper, Laurent M, additional, Carvalheiro, Tiago, additional, Vazirpanah, Nadia, additional, Silva-Cardoso, Sandra, additional, Affandi, Alsya J, additional, Chouri, Eleni, additional, v.d Kroef, Maarten, additional, Tieland, Ralph G, additional, Bekker, Cornelis P J, additional, Wichers, Catharina G K, additional, Rossato, Marzia, additional, Mocholi-Gimeno, Enric, additional, Tekstra, Janneke, additional, Ton, Evelien, additional, van Laar, Jaap M, additional, Cossu, Marta, additional, Beretta, Lorenzo, additional, Garcia Perez, Samuel, additional, Pandit, Aridaman, additional, Bonte-Mineur, Femke, additional, Reedquist, Kris A, additional, van den Bogaart, Geert, additional, Radstake, Timothy R D J, additional, and Marut, Wioleta, additional

Published
2021
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18. Cytokine receptor clustering in sensory neurons with an engineered cytokine fusion protein triggers unique pain resolution pathways

Author

IRAS OH Toxicology, dIRAS RA-1, Prado, Judith, Westerink, Remco H S, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Pandit, Aridaman, Versteeg, Sabine, van de Worp, Wouter, Kanters, Deon H A J, Reedquist, Kris A, Koenderman, Leo, Hack, C Erik, Eijkelkamp, Niels, IRAS OH Toxicology, dIRAS RA-1, Prado, Judith, Westerink, Remco H S, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Pandit, Aridaman, Versteeg, Sabine, van de Worp, Wouter, Kanters, Deon H A J, Reedquist, Kris A, Koenderman, Leo, Hack, C Erik, and Eijkelkamp, Niels

Published
2021

19. Cytokine receptor clustering in sensory neurons with an engineered cytokine fusion protein triggers unique pain resolution pathways

Author

CTI Eijkelkamp, Infection & Immunity, Cancer, Regenerative Medicine and Stem Cells, Lab Reumatologie/Klinische Immunologie, CTI Pandit, Translationele immunologie, Experimentele Afdeling Longziekten, CTI, Brain, Child Health, Prado, Judith, Westerink, Remco H S, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Pandit, Aridaman, Versteeg, Sabine, van de Worp, Wouter, Kanters, Deon H A J, Reedquist, Kris A, Koenderman, Leo, Hack, C Erik, Eijkelkamp, Niels, CTI Eijkelkamp, Infection & Immunity, Cancer, Regenerative Medicine and Stem Cells, Lab Reumatologie/Klinische Immunologie, CTI Pandit, Translationele immunologie, Experimentele Afdeling Longziekten, CTI, Brain, Child Health, Prado, Judith, Westerink, Remco H S, Popov-Celeketic, Jelena, Steen-Louws, Cristine, Pandit, Aridaman, Versteeg, Sabine, van de Worp, Wouter, Kanters, Deon H A J, Reedquist, Kris A, Koenderman, Leo, Hack, C Erik, and Eijkelkamp, Niels

Published
2021

21. TOF-secondary ion mass spectrometry imaging of polymeric scaffolds with surrounding tissue after in vivo implantation

Author

Klerk, Leendert A., Dankers, Patricia Y.W., Popa, Eliane R., Bosman, Anton W., Sanders, Marjolein E., Reedquist, Kris A., and Heeren, Ron M.A.

Subjects
Polymers -- Chemical properties, Time-of-flight mass spectrometry -- Methods, Secondary ion mass spectrometry -- Methods, Imaging systems -- Methods, Imaging systems -- Technology application, Tissues -- Methods, Technology application, Chemistry
Abstract

Supramolecular polymeric materials are of increasing interest for the use as drug delivery carriers. A thorough insight in the biocompatibility and the degradation of these materials in vivo are of fundamental importance to further their development and application in medical practice. Molecular imaging techniques are powerful tools that enable the elucidation of molecular distributions in and around such polymer implants. A supramolecular polymeric hydrogel was implanted under the renal capsule to study its biocompatibility with TOF-SIMS. This results in a molecular cartography of the polymer implant combined with the cellular signature of the implantation environment. In this experiment, molecular signals are observed from cells that are involved in the biological response to the implant, e.g., macrophages. These molecular signatures are compared with macrophage standards cultured in different polarization environments. On the basis of this comparison, information can be acquired on the various macrophage differentiations that are connected to different stages in the foreign body response. Mass spectrometric imaging techniques offer the opportunity to visualize different histological phenomena in a single experiment without the need for specific immunohistochemical markers. Cellular infiltration into the polymer is visualized, offering a clear view on both biological and polymer features in a single imaging experiment. 10.1021/ac100837n

Published
2010

27. Selective involvement of ERK and JNK mitogen-activated protein kinases in early rheumatoid arthritis (1987 ACR criteria compared to 2010 ACR/EULAR criteria): a prospective study aimed at identification of diagnostic and prognostic biomarkers as well as therapeutic targets

Author

de Launay, Daphne, van de Sande, Marleen GH, de Hair, Maria JH, Grabiec, Aleksander M, van de Sande, Gijs PM, Lehmann, K Aad, Wijbrandts, Carla A, van Baarsen, Lisa GM, Gerlag, Danielle M, Tak, Paul P, and Reedquist, Kris A

Published
2012
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37. Induction of Inflammation and Fibrosis by Semaphorin 4A in Systemic Sclerosis

Author

Carvalheiro, Tiago, Affandi, Alsya J., Malvar Fernandez, B, Dullemond, Ilse, Cossu, Marta, Ottria, Andrea, Mertens, Jorre S., Giovannone, Barbara, Bonte-Mineur, Femke, Kok, Marc R., Marut, Wioleta, Reedquist, Kris A., Radstake, Timothy R., Garcia Perez, Samuel, Carvalheiro, Tiago, Affandi, Alsya J., Malvar Fernandez, B, Dullemond, Ilse, Cossu, Marta, Ottria, Andrea, Mertens, Jorre S., Giovannone, Barbara, Bonte-Mineur, Femke, Kok, Marc R., Marut, Wioleta, Reedquist, Kris A., Radstake, Timothy R., and Garcia Perez, Samuel

Published
2019

38. Histone modifications underlie monocyte dysregulation in patients with systemic sclerosis, underlining the treatment potential of epigenetic targeting

Author

Van Der Kroef, Maarten, Castellucci, Monica, Mokry, Michal, Cossu, Marta, Garonzi, Marianna, Bossini-Castillo, Lara M., Chouri, Eleni, Wichers, Catharina G.K., Beretta, Lorenzo, Trombetta, Elena, Silva-Cardoso, Sandra, Vazirpanah, Nadia, Carvalheiro, Tiago, Angiolilli, Chiara, Bekker, Cornelis P.J., Affandi, Alsya J., Reedquist, Kris A., Bonte-Mineur, Femke, Zirkzee, Els J.M., Bazzoni, Flavia, Radstake, Timothy R.D.J., Rossato, Marzia, Van Der Kroef, Maarten, Castellucci, Monica, Mokry, Michal, Cossu, Marta, Garonzi, Marianna, Bossini-Castillo, Lara M., Chouri, Eleni, Wichers, Catharina G.K., Beretta, Lorenzo, Trombetta, Elena, Silva-Cardoso, Sandra, Vazirpanah, Nadia, Carvalheiro, Tiago, Angiolilli, Chiara, Bekker, Cornelis P.J., Affandi, Alsya J., Reedquist, Kris A., Bonte-Mineur, Femke, Zirkzee, Els J.M., Bazzoni, Flavia, Radstake, Timothy R.D.J., and Rossato, Marzia

Published
2019

39. Induction of Inflammation and Fibrosis by Semaphorin 4A in Systemic Sclerosis

Author

UMC Utrecht, CTI Meyaard, Translationele immunologie, Infection & Immunity, Other research (not in main researchprogram), Lab Dermatologie/Allergologie, CTI Radstake, Carvalheiro, Tiago, Affandi, Alsya J., Malvar Fernandez, B, Dullemond, Ilse, Cossu, Marta, Ottria, Andrea, Mertens, Jorre S., Giovannone, Barbara, Bonte-Mineur, Femke, Kok, Marc R., Marut, Wioleta, Reedquist, Kris A., Radstake, Timothy R., Garcia Perez, Samuel, UMC Utrecht, CTI Meyaard, Translationele immunologie, Infection & Immunity, Other research (not in main researchprogram), Lab Dermatologie/Allergologie, CTI Radstake, Carvalheiro, Tiago, Affandi, Alsya J., Malvar Fernandez, B, Dullemond, Ilse, Cossu, Marta, Ottria, Andrea, Mertens, Jorre S., Giovannone, Barbara, Bonte-Mineur, Femke, Kok, Marc R., Marut, Wioleta, Reedquist, Kris A., Radstake, Timothy R., and Garcia Perez, Samuel

Published
2019

40. Histone modifications underlie monocyte dysregulation in patients with systemic sclerosis, underlining the treatment potential of epigenetic targeting

Author

Translationele immunologie, Other research (not in main researchprogram), MDL onderzoek 1, Child Health, Infection & Immunity, DBG Metabole en Endocriene Ziekten, CTI Meyaard, Van Der Kroef, Maarten, Castellucci, Monica, Mokry, Michal, Cossu, Marta, Garonzi, Marianna, Bossini-Castillo, Lara M., Chouri, Eleni, Wichers, Catharina G.K., Beretta, Lorenzo, Trombetta, Elena, Silva-Cardoso, Sandra, Vazirpanah, Nadia, Carvalheiro, Tiago, Angiolilli, Chiara, Bekker, Cornelis P.J., Affandi, Alsya J., Reedquist, Kris A., Bonte-Mineur, Femke, Zirkzee, Els J.M., Bazzoni, Flavia, Radstake, Timothy R.D.J., Rossato, Marzia, Translationele immunologie, Other research (not in main researchprogram), MDL onderzoek 1, Child Health, Infection & Immunity, DBG Metabole en Endocriene Ziekten, CTI Meyaard, Van Der Kroef, Maarten, Castellucci, Monica, Mokry, Michal, Cossu, Marta, Garonzi, Marianna, Bossini-Castillo, Lara M., Chouri, Eleni, Wichers, Catharina G.K., Beretta, Lorenzo, Trombetta, Elena, Silva-Cardoso, Sandra, Vazirpanah, Nadia, Carvalheiro, Tiago, Angiolilli, Chiara, Bekker, Cornelis P.J., Affandi, Alsya J., Reedquist, Kris A., Bonte-Mineur, Femke, Zirkzee, Els J.M., Bazzoni, Flavia, Radstake, Timothy R.D.J., and Rossato, Marzia

Published
2019

43. Additional file 2: of Control of cytokine mRNA degradation by the histone deacetylase inhibitor ITF2357 in rheumatoid arthritis fibroblast-like synoviocytes: beyond transcriptional regulation

Author

Angiolilli, Chiara, Kabala, Pawel, Grabiec, Aleksander, Rossato, Marzia, Wi Lai, Fossati, Gianluca, Mascagni, Paolo, SteinkĂźhler, Christian, Blackshear, Perry, Reedquist, Kris, Baeten, Dominique, and Radstake, Timothy

Abstract

Figure S2. Effects of ITF2357 on mRNA stability. (PDF 816 kb)

Published
2018
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44. Additional file 1: of Control of cytokine mRNA degradation by the histone deacetylase inhibitor ITF2357 in rheumatoid arthritis fibroblast-like synoviocytes: beyond transcriptional regulation

Author

Angiolilli, Chiara, Kabala, Pawel, Grabiec, Aleksander, Rossato, Marzia, Wi Lai, Fossati, Gianluca, Mascagni, Paolo, SteinkĂźhler, Christian, Blackshear, Perry, Reedquist, Kris, Baeten, Dominique, and Radstake, Timothy

Abstract

Figure S1. Kinetics of mRNA regulation by ITF2357. (PDF 293 kb)

Published
2018
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45. Additional file 3: of Control of cytokine mRNA degradation by the histone deacetylase inhibitor ITF2357 in rheumatoid arthritis fibroblast-like synoviocytes: beyond transcriptional regulation

Author

Angiolilli, Chiara, Kabala, Pawel, Grabiec, Aleksander, Rossato, Marzia, Wi Lai, Fossati, Gianluca, Mascagni, Paolo, SteinkĂźhler, Christian, Blackshear, Perry, Reedquist, Kris, Baeten, Dominique, and Radstake, Timothy

Abstract

Figure S3. TTP post-translational changes after ITF2357 treatment. (PDF 283 kb)

Published
2018
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46. Additional file 4: of Control of cytokine mRNA degradation by the histone deacetylase inhibitor ITF2357 in rheumatoid arthritis fibroblast-like synoviocytes: beyond transcriptional regulation

Author

Angiolilli, Chiara, Kabala, Pawel, Grabiec, Aleksander, Rossato, Marzia, Wi Lai, Fossati, Gianluca, Mascagni, Paolo, SteinkĂźhler, Christian, Blackshear, Perry, Reedquist, Kris, Baeten, Dominique, and Radstake, Timothy

Subjects
body regions, nervous system, fungi
Abstract

Sequences of primers. (PDF 111 kb)

Published
2018
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47. Induction of Inflammation and Fibrosis by Semaphorin 4A in Systemic Sclerosis

Author

Carvalheiro, Tiago, primary, Affandi, Alsya J., additional, Malvar‐Fernández, Beatriz, additional, Dullemond, Ilse, additional, Cossu, Marta, additional, Ottria, Andrea, additional, Mertens, Jorre S., additional, Giovannone, Barbara, additional, Bonte‐Mineur, Femke, additional, Kok, Marc R., additional, Marut, Wioleta, additional, Reedquist, Kris A., additional, Radstake, Timothy R., additional, and García, Samuel, additional

Published
2019
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48. Promotion of macrophage activation by Tie2 in the context of the inflamed synovia of rheumatoid arthritis and psoriatic arthritis patients

Author

Kabala, Pawel A, primary, Malvar-Fernández, Beatriz, additional, Lopes, Ana P, additional, Carvalheiro, Tiago, additional, Hartgring, Sarita A Y, additional, Tang, Man Wai, additional, Conde, Carmen, additional, Baeten, Dominique L, additional, Sleeman, Matthew, additional, Tak, Paul P, additional, Connor, Jane, additional, Radstake, Timothy R, additional, Reedquist, Kris A, additional, and García, Samuel, additional

Published
2019
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49. Histone modifications underlie monocyte dysregulation in patients with systemic sclerosis, underlining the treatment potential of epigenetic targeting

Author

van der Kroef, Maarten, primary, Castellucci, Monica, additional, Mokry, Michal, additional, Cossu, Marta, additional, Garonzi, Marianna, additional, Bossini-Castillo, Lara M, additional, Chouri, Eleni, additional, Wichers, Catharina G K, additional, Beretta, Lorenzo, additional, Trombetta, Elena, additional, Silva-Cardoso, Sandra, additional, Vazirpanah, Nadia, additional, Carvalheiro, Tiago, additional, Angiolilli, Chiara, additional, Bekker, Cornelis P J, additional, Affandi, Alsya J, additional, Reedquist, Kris A, additional, Bonte-Mineur, Femke, additional, Zirkzee, Els J M, additional, Bazzoni, Flavia, additional, Radstake, Timothy R D J, additional, and Rossato, Marzia, additional

Published
2019
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