Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New Pathway
Rheumatoid arthritis (RA) has an inflammatory milieu in the synovial compartment, which is regulated by a complex cytokine and chemokine network that induces continuously degenerative and inflammatory reactions. The secreted osteoclastogenic factor of activated T cells (SOFAT) is a unique cytokine a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01442/full |
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| author | Marcelo Henrique Napimoga Weslley Danny Dantas Formiga Henrique Ballassini Abdalla Carlos Antônio Trindade-da-Silva Camila Motta Venturin Elizabeth Ferreira Martinez Ana Carolina Rossaneis Waldiceu A. Verri Juliana Trindade Clemente-Napimoga |
| author_facet | Marcelo Henrique Napimoga Weslley Danny Dantas Formiga Henrique Ballassini Abdalla Carlos Antônio Trindade-da-Silva Camila Motta Venturin Elizabeth Ferreira Martinez Ana Carolina Rossaneis Waldiceu A. Verri Juliana Trindade Clemente-Napimoga |
| author_sort | Marcelo Henrique Napimoga |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) has an inflammatory milieu in the synovial compartment, which is regulated by a complex cytokine and chemokine network that induces continuously degenerative and inflammatory reactions. The secreted osteoclastogenic factor of activated T cells (SOFAT) is a unique cytokine and represents an alternative pathway for osteoclast activation. In this study, we examined whether SOFAT is able to induce joint pain and investigated the presence of SOFAT in a Collagen-induced Arthritis (CIA) model and in human subjects. Here, we found that an intra-articular stimulation with SOFAT (1, 10, 100, or 1,000 ng/10 μl) in the knee joint significantly decreases the mechanical threshold in the hind paw of mice (p < 0.05). Moreover, after a second injection of SOFAT, the mechanical threshold decrease was sustained for up to 8 days (p < 0.05). In the CIA model, the immunohistochemical assay of knee joint showed positivity stained for SOFAT, and the mRNA and protein expression of SOFAT were significantly higher in the affected-group (p < 0.05). Besides, the mRNA of RANKL, IL-1β, IL-6, and IL-15 were significantly higher in the affected-group (p < 0.05). Finally, SOFAT was detected in the synovial fluid of RA patients, but not in OA patients (p < 0.05). In conclusion, SOFAT is up regulated in inflammatory milieu such as RA but not in non-inflammatory OA. SOFAT may be a novel molecule in the complex inflammatory phenotype of RA. |
| first_indexed | 2024-12-23T05:22:00Z |
| format | Article |
| id | doaj.art-041d9a6a6d2041d1903d6823eb64cf30 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T05:22:00Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-041d9a6a6d2041d1903d6823eb64cf302022-12-21T17:58:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01442536645Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New PathwayMarcelo Henrique Napimoga0Weslley Danny Dantas Formiga1Henrique Ballassini Abdalla2Carlos Antônio Trindade-da-Silva3Camila Motta Venturin4Elizabeth Ferreira Martinez5Ana Carolina Rossaneis6Waldiceu A. Verri7Juliana Trindade Clemente-Napimoga8Laboratoy of Neuroimmune Interface of Pain Research, Faculdade São Leopoldo Mandic, Instituto de Pesquisas São Leopoldo Mandic, Campinas, BrazilLaboratoy of Neuroimmune Interface of Pain Research, Faculdade São Leopoldo Mandic, Instituto de Pesquisas São Leopoldo Mandic, Campinas, BrazilLaboratoy of Neuroimmune Interface of Pain Research, Faculdade São Leopoldo Mandic, Instituto de Pesquisas São Leopoldo Mandic, Campinas, BrazilLaboratoy of Neuroimmune Interface of Pain Research, Faculdade São Leopoldo Mandic, Instituto de Pesquisas São Leopoldo Mandic, Campinas, BrazilFaculdade São Leopoldo Mandic, Instituto São Leopoldo Mandic, Campinas, BrazilFaculdade São Leopoldo Mandic, Instituto São Leopoldo Mandic, Campinas, BrazilDepartamento de Ciências Patológicas, Universidade Estadual de Londrina, Londrina, BrazilDepartamento de Ciências Patológicas, Universidade Estadual de Londrina, Londrina, BrazilLaboratoy of Neuroimmune Interface of Pain Research, Faculdade São Leopoldo Mandic, Instituto de Pesquisas São Leopoldo Mandic, Campinas, BrazilRheumatoid arthritis (RA) has an inflammatory milieu in the synovial compartment, which is regulated by a complex cytokine and chemokine network that induces continuously degenerative and inflammatory reactions. The secreted osteoclastogenic factor of activated T cells (SOFAT) is a unique cytokine and represents an alternative pathway for osteoclast activation. In this study, we examined whether SOFAT is able to induce joint pain and investigated the presence of SOFAT in a Collagen-induced Arthritis (CIA) model and in human subjects. Here, we found that an intra-articular stimulation with SOFAT (1, 10, 100, or 1,000 ng/10 μl) in the knee joint significantly decreases the mechanical threshold in the hind paw of mice (p < 0.05). Moreover, after a second injection of SOFAT, the mechanical threshold decrease was sustained for up to 8 days (p < 0.05). In the CIA model, the immunohistochemical assay of knee joint showed positivity stained for SOFAT, and the mRNA and protein expression of SOFAT were significantly higher in the affected-group (p < 0.05). Besides, the mRNA of RANKL, IL-1β, IL-6, and IL-15 were significantly higher in the affected-group (p < 0.05). Finally, SOFAT was detected in the synovial fluid of RA patients, but not in OA patients (p < 0.05). In conclusion, SOFAT is up regulated in inflammatory milieu such as RA but not in non-inflammatory OA. SOFAT may be a novel molecule in the complex inflammatory phenotype of RA.https://www.frontiersin.org/article/10.3389/fimmu.2020.01442/fullinflammationSOFATrheumatoid arthritispainosteoclast |
| spellingShingle | Marcelo Henrique Napimoga Weslley Danny Dantas Formiga Henrique Ballassini Abdalla Carlos Antônio Trindade-da-Silva Camila Motta Venturin Elizabeth Ferreira Martinez Ana Carolina Rossaneis Waldiceu A. Verri Juliana Trindade Clemente-Napimoga Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New Pathway Frontiers in Immunology inflammation SOFAT rheumatoid arthritis pain osteoclast |
| title | Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New Pathway |
| title_full | Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New Pathway |
| title_fullStr | Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New Pathway |
| title_full_unstemmed | Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New Pathway |
| title_short | Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New Pathway |
| title_sort | secreted osteoclastogenic factor of activated t cells sofat is associated with rheumatoid arthritis and joint pain initial evidences of a new pathway |
| topic | inflammation SOFAT rheumatoid arthritis pain osteoclast |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01442/full |
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