Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New Pathway

Author(s)

Napimoga, Marcelo Henrique ^[1] ; Dantas Formiga, Weslley Danny ^[1] ; Abdalla, Henrique Ballassini ^[1] ; Trindade-da-Silva, Carlos Antonio ^[1] ; Venturin, Camila Motta ^[2] ; Martinez, Elizabeth Ferreira ^[2] ; Rossaneis, Ana Carolina ^[3] ; Verri Jr, Waldiceu A. ; Clemente-Napimoga, Juliana Trindade ^[1]

Affiliation

^[1] Fac Sao Leopoldo Mandic, Inst Pesquisas Sao Leopoldo Mandic, Laboratoy Neuroimmune Interface Pain Res, Campinas, SP - Brazil

^[2] Fac Sao Leopoldo Mandic, Inst Sao Leopoldo Mandic, Campinas, SP - Brazil

^[3] Univ Estadual Londrina, Dept Ciencias Patol, Londrina - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 11, JUL 28 2020.
• Web of Science Citations: 0

Abstract

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 mu l) 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-1 beta, 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. (AU)

• FAPESP's process: 13/09524-2 - Evaluation of the effects of the cytokine SOFAT on osteoblast cells and its potential on bone inflammatory diseases
• Grantee: Marcelo Henrique Napimoga
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/22334-9 - Use of drug delivery systems for the development and application of anti-inflammatory agents with potential immunomodulatory and neuroprotective effects
• Grantee: Marcelo Henrique Napimoga
• Support Opportunities: Research Projects - Thematic Grants