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 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.
Highlights
The term arthritis is used to refer to a group of diseases that affect the joints with varied degrees of inflammation in sterile and septic forms [1, 2]
A new cytokine was described, namely, Secreted Osteoclastogenic Factor of Activated T cells (SOFAT), which is capable of inducing osteoclast formation in a RANKL-independent manner [11]
We demonstrated that secreted osteoclastogenic factor of activated T cells (SOFAT) is an important elicitor of bone breakdown when directly injected in mice, and elevated levels of SOFAT were found in inflamed gingival tissue from chronic periodontitis patients [19]
Summary
The term arthritis is used to refer to a group of diseases that affect the joints with varied degrees of inflammation in sterile and septic forms [1, 2]. Despite the well-recognized burdens of arthritis, such as pain, swelling, and stiffness, 60% of arthritis-affected report limitations in their daily activities [3]. SOFAT in RA Pathogenesis and society public cost since a high percentage of occurrence is in the working-age population (18–64 years old) [4, 5]. Within this set of diseases commonly called arthritis, osteoarthritis (OA) represents the highest incidence; rheumatoid arthritis (RA), gout, and fibromyalgia are relevant [6]. The continuously degenerative and inflammatory reactions result from an abnormal innate and adaptive immune responses primarily affecting the joints and extra-articular tissues [7]. RA or OA present destruction of cartilage and underlying bone despite their different etiologies and biological mechanism
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