Wnt signaling as a translational target in rheumatoid and psoriatic arthritis

Abstract Background Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are chronic inflammatory diseases mainly affecting joints. RA primarily targets the synovial joints and is characterized by cartilage and bone erosion, whereas PsA is associated with skin and nail psoriasis and is characteri...

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Main Authors: Gloria Riitano, Francesca Spinelli, Valeria Manganelli, Daniela Caissutti, Antonella Capozzi, Cristina Garufi, Tina Garofalo, Roberta Misasi, Maurizio Sorice, Fabrizio Conti, Agostina Longo, Cristiano Alessandri
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-025-06174-2
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author Gloria Riitano
Francesca Spinelli
Valeria Manganelli
Daniela Caissutti
Antonella Capozzi
Cristina Garufi
Tina Garofalo
Roberta Misasi
Maurizio Sorice
Fabrizio Conti
Agostina Longo
Cristiano Alessandri
author_facet Gloria Riitano
Francesca Spinelli
Valeria Manganelli
Daniela Caissutti
Antonella Capozzi
Cristina Garufi
Tina Garofalo
Roberta Misasi
Maurizio Sorice
Fabrizio Conti
Agostina Longo
Cristiano Alessandri
author_sort Gloria Riitano
collection DOAJ
description Abstract Background Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are chronic inflammatory diseases mainly affecting joints. RA primarily targets the synovial joints and is characterized by cartilage and bone erosion, whereas PsA is associated with skin and nail psoriasis and is characterized by erosive bone damage with an exuberant bone formation and soft tissue involvement. Recent evidence described the involvement of the Wnt pathway in the pathogenesis of these diseases. Thus, we aimed to analyze some components of Wnt signaling, i.e. DKK1, Wnt 5a and β-catenin, and their association with disease activity indices, investigating possible differences between the two diseases. Methods Sera from 18 RA patients naïve for biological therapy, 18 PsA patients and 20 matched healthy donors (HD) were tested for DKK1 by ELISA, Wnt 5a and β-catenin by Immunoblotting. Values were correlated with CTX-1, detected by ELISA, and with disease activity indices: Disease Activity Score on 28 joints (DAS28-CRP) for RA and the Disease Activity in Psoriatic Arthritis (DAPSA) score for PsA. Results This study highlights significant increase in DKK1, Wnt 5a, and β-catenin levels in RA and PsA patients compared to HD, with distinct patterns of correlation with disease activity indices. Indeed, in RA patients, DKK1 levels positively correlated with DAS28-CRP score, whereas in PsA patients, DKK1 levels negatively correlated with DAPSA score. Our findings showed a strong correlation between DKK1 and CTX-1 levels in RA patients, supporting the relationship between DKK1 levels and the presence of joint erosions. Furthermore, a significant positive correlation was found between β-catenin and IL-6 levels in RA, indicating that β-catenin may be involved in the inflammatory cascade. Conclusion This study compares the involvement of Wnt signaling in RA and PsA, suggesting that Wnt signaling may represent a possible mechanism of disease activity. In particular, it indicates that DKK1 levels are correlated with CTX-1, a marker of bone resorption, and with disease activity in RA patients. These findings underscore the importance of these biomarkers in the potential monitoring of patients, offering insights into disease mechanisms and potential therapeutic targets.
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spelling doaj-art-0665e1e8993840a787badf23bd5d93d62025-02-09T12:52:32ZengBMCJournal of Translational Medicine1479-58762025-02-0123111010.1186/s12967-025-06174-2Wnt signaling as a translational target in rheumatoid and psoriatic arthritisGloria Riitano0Francesca Spinelli1Valeria Manganelli2Daniela Caissutti3Antonella Capozzi4Cristina Garufi5Tina Garofalo6Roberta Misasi7Maurizio Sorice8Fabrizio Conti9Agostina Longo10Cristiano Alessandri11Department of Experimental Medicine, “Sapienza” University of RomeRheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of RomeDepartment of Experimental Medicine, “Sapienza” University of RomeDepartment of Experimental Medicine, “Sapienza” University of RomeDepartment of Experimental Medicine, “Sapienza” University of RomeRheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of RomeDepartment of Experimental Medicine, “Sapienza” University of RomeDepartment of Experimental Medicine, “Sapienza” University of RomeDepartment of Experimental Medicine, “Sapienza” University of RomeRheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of RomeDepartment of Experimental Medicine, “Sapienza” University of RomeRheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, “Sapienza” University of RomeAbstract Background Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are chronic inflammatory diseases mainly affecting joints. RA primarily targets the synovial joints and is characterized by cartilage and bone erosion, whereas PsA is associated with skin and nail psoriasis and is characterized by erosive bone damage with an exuberant bone formation and soft tissue involvement. Recent evidence described the involvement of the Wnt pathway in the pathogenesis of these diseases. Thus, we aimed to analyze some components of Wnt signaling, i.e. DKK1, Wnt 5a and β-catenin, and their association with disease activity indices, investigating possible differences between the two diseases. Methods Sera from 18 RA patients naïve for biological therapy, 18 PsA patients and 20 matched healthy donors (HD) were tested for DKK1 by ELISA, Wnt 5a and β-catenin by Immunoblotting. Values were correlated with CTX-1, detected by ELISA, and with disease activity indices: Disease Activity Score on 28 joints (DAS28-CRP) for RA and the Disease Activity in Psoriatic Arthritis (DAPSA) score for PsA. Results This study highlights significant increase in DKK1, Wnt 5a, and β-catenin levels in RA and PsA patients compared to HD, with distinct patterns of correlation with disease activity indices. Indeed, in RA patients, DKK1 levels positively correlated with DAS28-CRP score, whereas in PsA patients, DKK1 levels negatively correlated with DAPSA score. Our findings showed a strong correlation between DKK1 and CTX-1 levels in RA patients, supporting the relationship between DKK1 levels and the presence of joint erosions. Furthermore, a significant positive correlation was found between β-catenin and IL-6 levels in RA, indicating that β-catenin may be involved in the inflammatory cascade. Conclusion This study compares the involvement of Wnt signaling in RA and PsA, suggesting that Wnt signaling may represent a possible mechanism of disease activity. In particular, it indicates that DKK1 levels are correlated with CTX-1, a marker of bone resorption, and with disease activity in RA patients. These findings underscore the importance of these biomarkers in the potential monitoring of patients, offering insights into disease mechanisms and potential therapeutic targets.https://doi.org/10.1186/s12967-025-06174-2Rheumatoid arthritisPsoriatic arthritisWnt signalingDKK1β-catenin
spellingShingle Gloria Riitano
Francesca Spinelli
Valeria Manganelli
Daniela Caissutti
Antonella Capozzi
Cristina Garufi
Tina Garofalo
Roberta Misasi
Maurizio Sorice
Fabrizio Conti
Agostina Longo
Cristiano Alessandri
Wnt signaling as a translational target in rheumatoid and psoriatic arthritis
Journal of Translational Medicine
Rheumatoid arthritis
Psoriatic arthritis
Wnt signaling
DKK1
β-catenin
title Wnt signaling as a translational target in rheumatoid and psoriatic arthritis
title_full Wnt signaling as a translational target in rheumatoid and psoriatic arthritis
title_fullStr Wnt signaling as a translational target in rheumatoid and psoriatic arthritis
title_full_unstemmed Wnt signaling as a translational target in rheumatoid and psoriatic arthritis
title_short Wnt signaling as a translational target in rheumatoid and psoriatic arthritis
title_sort wnt signaling as a translational target in rheumatoid and psoriatic arthritis
topic Rheumatoid arthritis
Psoriatic arthritis
Wnt signaling
DKK1
β-catenin
url https://doi.org/10.1186/s12967-025-06174-2
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