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

Zhang, Xuepei; Ma, Jin; Mo, Yujun; Jing, Jun; Zheng, Dong-Hui; Chen, Le‐Feng; Wu, Tao Cheng; Chen, Chutao; Zhang, Qian; Zou, Yaoyao; Lin, Jianwen; Xu, Yanhui; Zou, Yao-Wei; Yang, Zehong; Li, Ling; Miossec, Pierre; Dai, Lie

doi:10.3389/fimmu.2021.778480

Cited by 4 publications

(7 citation statements)

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“…When the cells reached confluence (5-7 days), they were passaged. Cells were considered FLS when a typical spindle-shaped, fibroblast-like appearance was present and the positive rate for the surface marker CD90 ( Manferdini et al, 2016 ; Zhang et al, 2021 ) was >90%. FLS at passages 3-6 were used for subsequent experiments.…”

Section: Methodsmentioning

confidence: 99%

RUNX1 Ameliorates Rheumatoid Arthritis Progression through Epigenetic Inhibition of LRRC15

Ding

Mei

et al. 2023

Molecules and Cells

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Leucine-rich repeat containing 15 (LRRC15) has been identified as a contributing factor for cartilage damage in osteoarthritis; however, its involvement in rheumatoid arthritis (RA) and the underlying mechanisms have not been well characterized. The purpose of this study was to explore the function of LRRC15 in RA-associated fibroblastlike synoviocytes (RA-FLS) and in mice with collagen-induced arthritis (CIA) and to dissect the epigenetic mechanisms involved. LRRC15 was overexpressed in the synovial tissues of patients with RA, and LRRC15 overexpression was associated with increased proliferative, migratory, invasive, and angiogenic capacities of RA-FLS and accelerated release of pro-inflammatory cytokines. LRRC15 knockdown significantly inhibited synovial proliferation and reduced bone invasion and destruction in CIA mice. Runt-related transcription factor 1 (RUNX1) transcriptionally represses LRRC15 by binding to core-binding factor subunit beta (CBF-β). Overexpression of RUNX1 significantly inhibited the invasive phenotype of RA-FLS and suppressed the expression of proinflammatory cytokines. Conversely, the effects of RUNX1 were significantly reversed after overexpression of LRRC15 or inhibition of RUNX1-CBF-β interactions. Therefore, we demonstrated that RUNX1-mediated transcriptional repression of LRRC15 inhibited the development of RA, which may have therapeutic effects for RA patients.

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Section: Methodsmentioning

confidence: 99%

RUNX1 Ameliorates Rheumatoid Arthritis Progression through Epigenetic Inhibition of LRRC15

Ding

Mei

et al. 2023

Molecules and Cells

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“…Consecutive RA patients aged ≥ 16 years and fulfilled the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA ( 12 ) were recruited between July 2015 to February 2019 from a real-world prospective cohort as described in our previous reports ( 4 , 13 ). Exclusion criteria were as follows: overlapping other autoimmune diseases (e.g.…”

Section: Methodsmentioning

confidence: 99%

“…All patients were treated according to the ACR/EULAR recommendations of ‘treat-to-target’ strategy and completed at least one-year follow up. Available demographic and clinical data were collected at baseline and visited at 3, 6, 9 and 12 months as in our previous reports ( 4 , 13 ), including age, gender, smoking habits, body mass index (BMI), disease duration, disease activity, physical function, radiographic indicators and medications.…”

Section: Methodsmentioning

confidence: 99%

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Myokine myostatin is a novel predictor of one-year radiographic progression in patients with rheumatoid arthritis: A prospective cohort study

Lin

Ma²,

Yang³

et al. 2022

Front. Immunol.

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BackgroundAssociations between rheumatoid arthritis (RA) and reduced skeletal muscle have been studied, and we firstly reported myopenia independently predict one-year radiographic progression in RA. Myokine myostatin can negatively regulate skeletal muscle mass and promote osteoclast differentiation. However, there is no report about their relationships in RA patients. We firstly explored the relationship of serum myostatin and disease characteristics, as well as aggravated joint destruction during one-year follow-up.MethodsConsecutive RA patients were recruited from a real-world prospective cohort and completed at least one-year follow-up. Baseline serum level of myostatin was measured by enzyme-linked immunosorbent assay. Clinical data in RA patients as well as muscle index in both RA patients and healthy controls were collected. One-year radiographic progression as primary outcome was defined by a change in the total Sharp/van der Heijde modified score ≥0.5 units.ResultsTotally 344 RA patients (age 47.9 ± 12.5 years, 84.0% female) and 118 healthy control subjects (age 42.8 ± 11.3 years, 74.6% female) were recruited. Compared with healthy controls, RA patients showed a higher level of serum myostatin at baseline (3.241 ± 1.679 ng/ml vs. 1.717 ± 0.872 ng/ml, P<0.001), although lower appendicular skeletal muscle mass index (ASMI, 6.0 ± 0.9 kg/m2vs. 6.5 ± 1.0 kg/m2, P<0.001). In RA patients, those with high myostatin level showed a higher rate of radiographic progression than low myostatin group (45.3% vs. 18.6%, P<0.001). Furtherly, RA patients were stratified into four subgroups according to serum myostatin and myopenia. Compared with other three subgroups, RA patients with high myostatin overlapping myopenia had the highest rate of radiographic progression (67.2% vs. 10.3%-31.4%, P<0.001), as well as the lowest proportion of remission and the highest rate of physical dysfunction during one-year follow-up. After adjustment for confounding factors, high serum myostatin (AOR=3.451, 95%CI: 2.016-5.905) and myopenia (AOR=2.387, 95%CI: 1.416-4.022) at baseline were risk factors for one-year radiographic progression, especially for those with high myostatin overlapping myopenia (AOR=10.425, 95%CI: 3.959-27.450) as the highest-risk individuals among four subgroups. Significant synergistic interaction effect was observed between high myostatin and myopenia on one-year radiographic progression (AP=66.3%, 95%CI: 43.2%-89.3%).ConclusionMyostatin is a novel predictor of aggravated joint destruction in RA patients which has synergistic interaction with myopenia for predicting value.

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“…Previously, fibroblasts were considered to be a homogeneous cell population, while emerging evidence indicates that fibroblasts can serve as a reservoir that can provide tissue-specialized fibroblasts and pathological fibroblasts in disease. 17 In AS, with THY1 (also known as CD90), 19 vimentin, 20 alpha smooth muscle actin, prolyl 4-hydroxylase β, 21 S100A4, etc., used as markers in recent studies, ASFs were reported to mainly regulate the inflammatory environment and mediate abnormal ossification. 22 First, similar to rheumatoid arthritis synovial fibroblasts (RASFs) in RA, ASFs can cause certain pathological responses in diseases by regulating factor secretion, coordinating inflammatory responses, regulating tissue homeostasis, and mediating joint remodeling.…”

Section: Fibroblasts In Asmentioning

confidence: 99%

Fibroblast Insights into the Pathogenesis of Ankylosing Spondylitis

Liu,

Cai,

et al. 2023

JIR

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Purpose of the Review: Emerging evidence has shown that ankylosing spondylitis fibroblasts (ASFs) act as crucial participants in inflammation and abnormal ossification in ankylosing spondylitis (AS). This review examines the investigations into ASFs and their pathological behavior, which contributes to inflammatory microenvironments and abnormal bone formation. The review spans the period from 2000 to 2023, with a primary focus on the most recent decade. Additionally, the review provides an in-depth discussion on studies on ASF ossification at the cellular level. Recent Findings: ASFs organize immune functions by recruiting immune cells and influencing their differentiation and activation, thus mediate the inflammatory response in the early phase of disease. ASFs promote joint destruction at sites of cartilage and actively promote abnormal ossification by recruiting osteoblasts, differentiation into myofibroblasts or ossification directly. Many signaling pathways and cytokines such as Wnt signaling and BMP/TGF-β signaling are involved in ASF ossification. Summary: ASFs play a key role in AS inflammation and osteogenesis. Further studies are required to elucidate molecular mechanisms behind that and provide new targets and directions for AS diagnosis and treatment from a new perspective of fibroblasts.

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

Cited by 4 publications

References 50 publications

RUNX1 Ameliorates Rheumatoid Arthritis Progression through Epigenetic Inhibition of LRRC15

RUNX1 Ameliorates Rheumatoid Arthritis Progression through Epigenetic Inhibition of LRRC15

Myokine myostatin is a novel predictor of one-year radiographic progression in patients with rheumatoid arthritis: A prospective cohort study

Fibroblast Insights into the Pathogenesis of Ankylosing Spondylitis

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