Fibroblast-like synoviocytes in rheumatoid arthritis: Surface markers and phenotypes

Wu, Zewen; Ma, Ding; Yang, Helin; Gao, Jinfang; Zhang, Gailian; Xu, Ke; Zhang, Liyun

doi:10.1016/j.intimp.2021.107392

Cited by 91 publications

(34 citation statements)

References 67 publications

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“…Moreover, galangin improved the histology of arthritis in vivo . The progression of RA was accompanied by the proliferation of RAFLSs, which secreted pro-inflammatory cytokines [ 5–7 , 25–28 ]. Previous studies have established that the development of the osteoclast-rich portion of the synovial membrane (pannus) of RA synovial joints increased the tumor risk [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…To date, RA treatment focuses only on pain relief and anti-inflammation medication to improve patients’ quality of life [ 4 ]. The primary parts of RA pathogenesis are the fibroblast-like synoviocytes in the joint synovial membrane [ 5 ]. The synovial membrane is vital in reducing the friction between the joint cartilages and to provide nutrients [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…The physiology of the fibroblast-like synoviocytes is significantly changed during RA progression, which presents as the loss of contact inhibition properties and over-proliferation events. Moreover, the fibroblast-like synoviocytes secrete various pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, which cause inflammation of the synovium, leading to the joints’ destruction [ 5–7 ]. There is, therefore, an urgent need to develop alternative drugs for RA.…”

Section: Introductionmentioning

confidence: 99%

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Galangin alleviates rheumatoid arthritis in rats by downregulating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway

Deng

Wan

et al. 2022

Bioengineered

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Rheumatoid arthritis (RA) is a chronic autoimmune disease that greatly affect patients’ quality of life. Galangin extract is renowned for its anti-proliferative and anti-oxidative characteristics. However, galangin cytotoxicity studies are presently inadequate. We aimed to investigate the therapeutic potential of galangin on RA by investigating the PI3K/AKT signaling pathway.Fibroblast-like synovial cells (FLSs) were exposed to lipopolysaccharide (LPS) to establish an RA model in vitro . An ELISA assay was used to detect the levels of IL-1β, TNF-α, and IL-6. Cell viability and apoptosis were determined by CCK8/EdU and flow cytometry assays. A western blot assay was used to analyze the protein expression levels. An RA rat model was established to evaluate the function of galangin through histopathological examination. Our results found that galangin induced apoptosis, inhibited cell proliferation, and increased cell invasion of rheumatoid arthritis fibroblast-like synovial cells (RAFLSs). Galangin inactivated the PI3K/AKT signaling pathway and the inflammatory response. An agonist of PI3K signaling, 740Y‐P, restored the cellular functions of RAFLSs. Moreover, galangin suppressed the development of RA in vivo . Galangin effected its anti-arthritic influence through the PI3K/AKT signaling pathway. Galangin has potential as an alternative treatment for RA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Galangin alleviates rheumatoid arthritis in rats by downregulating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway

Deng

Wan

et al. 2022

Bioengineered

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“…RA is a chronic autoimmune disease with synovitis and synovial hyperplasia as the main pathological features (Josef et al, 2018). The pathological process of RA involves a variety of cells, including B cells, T cells, macrophages, and FLS (McInnes and Schett, 2017;Wu et al, 2021). FLS is a highly specific mesenchymal cell that exists in the synovium of joints.…”

Section: Discussionmentioning

confidence: 99%

Anti-Rheumatoid Arthritic Effects of Paris Saponin VII in Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Adjuvant-Induced Arthritis in Rats

Meng

Yue

et al. 2021

Front. Pharmacol.

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In the pathogenesis of rheumatoid arthritis (RA), rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) have tumor-like characteristics, mainly manifested by hyperproliferation and resistance to apoptosis and then it will erode the bone and cartilage, eventually leading to joint destruction. Paris saponin VII (PS VII) is an active compound derived from a traditional herbal medicine named Trillium tschonoskii Maxim, which has anti-tumor, analgesic, and immunomodulatory effects. However, its anti-RA effect has not yet been reported. This study was to investigate the effect of PS VII on two rheumatoid arthritis fibroblast-like synoviocytes lines (RA-FLS and MH7A) and adjuvant-induced arthritis (AIA) in rats. In vitro, the effects of PS VII on the proliferation, cell cycle, and apoptosis of RA-FLS and MH7A cells were detected by MTT, flow cytometry, and western blot analysis. In vivo, the effect of PS VII on the weight of the rat, paw swelling, ankle joint diameter, arthritis index, serum inflammatory cytokines (TNF-α, IL-6, and IL-1β), histopathological assessment and apoptosis proteins in the synovial tissues were evaluated in AIA rats. The in vitro studies showed that PS VII inhibited the proliferation of RA-FLS and MH7A cells, induced S phase arrest and triggered cell apoptosis mainly through the mitochondrial apoptotic pathway and the regulation of JNK and p38 MAPK pathways. The in vivo studies revealed that PS VII could improve ameliorate body weight, paw swelling, ankle joint diameter, reduce the spleen and thymus index, suppress the production of TNF-α, IL-6 and IL-1β, improve histopathological changes and regulate the expressions of apoptosis proteins in AIA Rats. In conclusion, PS VII could inhibit the proliferation and trigger apoptosis of RA-FLS and MH7A cells by regulating the mitochondrial apoptosis pathway and the JNK and p38 MAPK pathways, and alleviate the symptoms of RA, signifying it to be one of the potential anti-RA therapeutics.

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“…Although the results obtained in the whole cohort were confirmed in the subgroup of treatment-naive RA, they need to be extended to patients with early and treatment-naïve disease in multicenter trials. Single-cell technology has identified various cell surface molecules to identify different fibroblast subsets, including cadherin-11, CD55, PDPN, FAP, CD90, and vimentin ( 50 ). The clinical significance of these different fibroblast subsets identified by markers other than CD90 needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Addition of Fibroblast-Stromal Cell Markers to Immune Synovium Pathotypes Better Predicts Radiographic Progression at 1 Year in Active Rheumatoid Arthritis

Zhang

et al. 2021

Front. Immunol.

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ObjectivesThis study aims to investigate if addition of fibroblast-stromal cell markers to a classification of synovial pathotypes improves their predictive value on clinical outcomes in rheumatoid arthritis (RA).MethodsActive RA patients with a knee needle synovial biopsy at baseline and finished 1-year follow-up were recruited from a real-world prospective cohort. Positive staining for CD20, CD38, CD3, CD68, CD31, and CD90 were scored semiquantitatively (0-4). The primary outcome was radiographic progression defined as a minimum increase of 0.5 units of the modified total Sharp score from baseline to 1 year.ResultsAmong 150 recruited RA patients, 123 (82%) had qualified synovial tissue. Higher scores of CD20+ B cells, sublining CD68+ macrophages, CD31+ endothelial cells, and CD90+ fibroblasts were associated with less decrease in disease activity and greater increase in radiographic progression. A new fibroblast-based classification of synovial pathotypes giving more priority to myeloid and stromal cells classified samples as myeloid-stromal (57.7%, 71/123), lymphoid (31.7%, 39/123), and paucicellular pathotypes (10.6%, 13/123). RA patients with myeloid-stromal pathotype showed the highest rate of radiographic progression (43.7% vs. 23.1% vs. 7.7%, p = 0.011), together with the lowest rate of Boolean remission at 3, 6, and 12 months. Baseline synovial myeloid-stromal pathotype independently predicted radiographic progression at 1 year (adjusted OR: 3.199, 95% confidence interval (95% CI): 1.278, 8.010). Similar results were obtained in a subgroup analysis of treatment-naive RA.ConclusionsThis novel fibroblast-based myeloid-stromal pathotype could predict radiographic progression at 1 year in active RA patients which may contribute to the shift of therapeutic decision in RA.

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Fibroblast-like synoviocytes in rheumatoid arthritis: Surface markers and phenotypes

Cited by 91 publications

References 67 publications

Galangin alleviates rheumatoid arthritis in rats by downregulating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway

Galangin alleviates rheumatoid arthritis in rats by downregulating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway

Anti-Rheumatoid Arthritic Effects of Paris Saponin VII in Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Adjuvant-Induced Arthritis in Rats

Addition of Fibroblast-Stromal Cell Markers to Immune Synovium Pathotypes Better Predicts Radiographic Progression at 1 Year in Active Rheumatoid Arthritis

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