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

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.

The role of secreted osteoclastogenic factor of activated T cells in bone remodeling

“…Likewise, in the collagen-induced arthritis (CIA) model, the immunohistochemistry of SOFAT exhibits high positive stains in the knee joint of mice. In agreement with this, the mRNA and protein expression of SOFAT are significantly higher in the joints of mice induced by the CIA protocol [32] . Moreover, SOFAT is highly expressed in inflammatory milieus, such as RA, not in non-inflammatory osteoarthritis (OA), suggesting that SOFAT might be a novel biological marker in the inflammatory diseases accompanied by lymphocytic infiltration [32] .…”

“…In agreement with this, the mRNA and protein expression of SOFAT are significantly higher in the joints of mice induced by the CIA protocol [32] . Moreover, SOFAT is highly expressed in inflammatory milieus, such as RA, not in non-inflammatory osteoarthritis (OA), suggesting that SOFAT might be a novel biological marker in the inflammatory diseases accompanied by lymphocytic infiltration [32] . In a word, SOFAT could be expressed in gingival tissues (periodontitis), osteolytic bone lesions, and the knee joint’s synovial liquid (RA).…”

“… [51] Arthritis Intra-articular injection of SOFAT in the mice knee joint SOFAT can induce joint pain. [32] Orthodontics Sample: rat teeth 1. Control group 2.…”

“…Recently, one original research has appointed that intra-articular injection with SOFAT in the knee joint could significantly decrease the mechanical threshold in the hind paw of mice ( Table 1 ). Particularly, this nociceptive response initiates after 3 h of injection, and a second injection assay could sustain this nociceptive stage for up to 8 days [32] . The delay in initiating the mechanical hyperalgesia may attribute to SOFAT does not stimulate neuronal fibers directly.…”

Influência do ômega 3 e da dexametasona em artrite induzida por adjuvante completo de freund CFA

“…Osteoartrite é uma forma de artrite, considerada uma doença degenerativa, inicialmente pela perda de cartilagem e remodelação óssea e causando inflamação sinovial (Napimoga et al, 2020). O desenvolvimento da OA é comum na articulação temporomandibular e pode causar dor e diminuição do espaço articular.…”