Fibroblast‐like synoviocytes: key effector cells in rheumatoid arthritis

Abstract

SummaryRheumatoid arthritis (RA) remains a significant unmet medical need despite significant therapeutic advances. The pathogenesis of RA is complex and includes many cell types, including T cells, B cells, and macrophages. Fibroblast-like synoviocytes (FLS) in the synovial intimal lining also play a key role by producing cytokines that perpetuate inflammation and proteases that contribute to cartilage destruction. Rheumatoid FLS develop a unique aggressive phenotype that increases invasiveness into the extracellular matrix and further exacerbates joint damage. Recent advances in understanding the biology of FLS, including their regulation regulate innate immune responses and activation of intracellular signaling mechanisms that control their behavior, provide novel insights into disease mechanisms. New agents that target FLS could potentially complement the current therapies without major deleterious effect on adaptive immune responses.

Activation of human fibroblast-like synoviocytes by uric acid crystals in rheumatoid arthritis

“…25 Remarkably, uric acid crystals can induce various inflammatory mediators including cytokines, chemokines, proteases and reactive oxygen species, thereby playing an important role in the development of inflammatory responses. 26 Uric acid crystals have been shown to stimulate dendritic cell maturation, enhance antigenspecific immune responses and directly activate T cells.…”

Bone Morphogenetic Protein 2 and Transforming Growth Factor β1 Inhibit the Expression of the Proinflammatory Cytokine IL-34 in Rheumatoid Arthritis Synovial Fibroblasts

“…1 Among the cells located in the inflamed joint, synovial fibroblasts are crucial players driving inflammation and bone erosion. 2 IL-34, 3 basically described as promoting monocyte proliferation and survival, and osteoclast differentiation, 4 is expressed by synovial fibroblasts of RA patients. Its expression, correlated with inflammation, the number of leucocytes and the severity of the synovitis, is upregulated by TNFα and IL-1β.…”

Norisoboldine alleviates joint destruction in rats with adjuvant-induced arthritis by reducing RANKL, IL-6, PGE2, and MMP-13 expression

“…Effects of NOR on IL-1β-induced RANKL, PGE 2 , and MMP-13 expressions in FLS from AIA rats It has been demonstrated that proliferative FLS in the synovial membranes of RA-affected joints participates in both the propagation of inflammation and joint destruction, as they can produce large amounts of proinflammatory mediators and enzymes, including IL-1, IL-6, TNF-α, PGE 2 , and MMPs [20][21][22] .…”

“…The tumor-like proliferation of RA-FLS is considered to be one of the major effectors of cartilage and bone destruction in RA. They have the ability to produce massive amounts of pro-inflammatory [20][21][22]26] . Therefore, FLS cells were isolated from AIA rats and used in the following studies.…”