1,25-Dihydroxyvitamin D3 Inhibits the RANKL Pathway and Impacts on the Production of Pathway-Associated Cytokines in Early Rheumatoid Arthritis

Objectives. To study effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on RANKL signaling pathway and pathway-associated cytokines in patients with rheumatoid arthritis (RA).Methods. Receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), IFN-γ, IL-6, TNF-α, IL-17, and IL-4 were examined in 54 patients with incipient RA using a cytometric bead array (CBA) or an enzyme-linked immunosorbent assay (ELISA).Results. After 72 hours of incubation of peripheral blood mononuclear cells (PBMCs) with 1,25(OH)2D3in RA patients, the levels of RANKL, TNF-α, IL-17 and IL-6 significantly decreased compared to those of the control. 1,25(OH)2D3had no significantly impact on the levels of OPG, RANKL/OPG, and IL-4.Conclusions. The present study demonstrated that 1,25(OH)2D3reduced the production of RANKL and the secretion of TNF-α, IL-17, and IL-6 in PBMCs of RA patients, which indicated that 1,25(OH)2D3might be able to decrease damage of cartilage and bone in RA patients by regulating the expression of RANKL signaling pathway and pathway-associated cytokines.

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The Effects of microRNA-515-5p on the Toll-Like Receptor 4 (TLR4)/JNK Signaling Pathway and WNT1-Inducible-Signaling Pathway Protein 1 (WISP-1) Expression in Rheumatoid Arthritis Fibroblast-Like Synovial (RAFLS) Cells Following Treatment with Receptor Activator of Nuclear Factor-kappa-B Ligand (RANKL)

Medical Science Monitor ◽

10.12659/msm.920611 ◽

2020 ◽

Vol 26 ◽

Cited By ~ 2

Author(s):

Dongfeng Cai ◽

Song Hong ◽

Jin Yang ◽

Peng San

Keyword(s):

Rheumatoid Arthritis ◽

Signaling Pathway ◽

Nuclear Factor Kappa B ◽

Nuclear Factor ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Jnk Signaling ◽

Nuclear Factor Kappa ◽

Receptor Activator ◽

Jnk Signaling Pathway

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The Relationship between Serum and Gene Expression Levels of RANK, RANKL and Osteoprotegerin Inflammatory Pathway with Unstable Angina: A Case-control Study

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v20i4.6957 ◽

2021 ◽

Author(s):

Alireza Farrokhian ◽

Mahtab Miraftab ◽

Minoo Chenari ◽

Hossein Akbari ◽

Hassan Nikoueinejad ◽

...

Keyword(s):

Gene Expression ◽

Unstable Angina ◽

Nuclear Factor Kappa B ◽

Mononuclear Cells ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Nuclear Factor ◽

Inflammatory Pathway ◽

Nuclear Factor Kappa ◽

Receptor Activator

Osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B (RANK) and receptor activator of nuclear factor-kappa B ligand (RANKL), the members of the tumor necrosis factor (TNF) family, have multiple effects on bone metabolism, endocrine functions and, as an inflammatory pathway, in the immune system. This study tried to determine the association of the OPG/RANKL/RANK axis with the severity of unstable angina (UA) as an inflammatory condition. Our study involved 50 patients with UA and 50 healthy people. Serum and peripheral blood mononuclear cells were isolated from all participants. Serum levels and gene expression of OPG, RANKL, and RANK in mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. For each patient with UA, the thrombolysis in myocardial infarction (TIMI) and the global registry of acute coronary events (GRACE) scores were determined to evaluate the severity of the disease. Then we analyzed the relation of OPG, RANKL, and RANK levels with TIMI and GRACE scores in patients with UA. Discriminate analysis was used to predict the combinational models of such factors on the prediction of UA. Serum levels of OPG and RANKL (p<0.001) and gene expression of RANKL (p<0.001) were significantly more in patients than those in healthy ones. No relation was seen between the OPG/RANKL/RANK axis and the severity of UA according to TIMI and GRACE scores. Our study shows that serum level, as well as gene expression of OPG/RANKL/RANK axis neither, predicts the occurrence of UA nor shows any relationship with its severity.

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CCAAT/enhancer-binding protein beta (C/EBPβ) is an important mediator of 1,25 dihydroxyvitamin D3 (1,25D3)-induced receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblasts

BMB Reports ◽

10.5483/bmbrep.2019.52.6.166 ◽

2019 ◽

Vol 52 (6) ◽

pp. 391-396 ◽

Cited By ~ 4

Author(s):

Sungsin Jo ◽

Yun Young Lee ◽

Jinil Han ◽

Young Lim Lee ◽

Subin Yoon ◽

...

Keyword(s):

Nuclear Factor Kappa B ◽

Binding Protein ◽

Nuclear Factor ◽

Rankl Expression ◽

Dihydroxyvitamin D3 ◽

1,25 Dihydroxyvitamin D3 ◽

Nuclear Factor Kappa ◽

Important Mediator ◽

Enhancer Binding Protein ◽

Receptor Activator

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SAT0086 Receptor Activator of Nuclear Factor Kappa-B Ligand (Rankl) and Sclerostin are Related to Joint Destruction in Early Rheumatoid Arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-eular.3338 ◽

2015 ◽

Vol 74 (Suppl 2) ◽

pp. 679.3-680

Author(s):

S. Rantapää-Dahlqvist ◽

A. Boman ◽

H. Kokkonen ◽

E. Berglin

Keyword(s):

Rheumatoid Arthritis ◽

Early Rheumatoid Arthritis ◽

Nuclear Factor Kappa B ◽

Joint Destruction ◽

Nuclear Factor ◽

Nuclear Factor Kappa ◽

Receptor Activator

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Using protein microarray reveals clinical correlation between self-perception of patient and the apoptosis-related proteins in rheumatoid arthritis

10.21203/rs.3.rs-39433/v1 ◽

2020 ◽

Author(s):

Jian-ting Wen ◽

Jian Liu ◽

Hui Jiang ◽

Lei Wan ◽

Ling Xin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mononuclear Cells ◽

Expression Profiles ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Self Perception ◽

Roc Curve Analysis ◽

Peripheral Blood Mononuclear ◽

Related Proteins ◽

Potential Biomarkers

Abstract Background: The most severe effects of rheumatoid arthritis (RA) are loss of physical function, which may have a significant impact on self-perception of patient (SPP). However, the inherent relationship between SPP and the key proteins is not clear. The aim of this study was to get an insight into SPP of RA in connection with the the apoptosis-related proteins. Methods: We set out to investigate changes of the apoptosis-related proteins expression in the peripheral blood mononuclear cells (PBMCs) of RA. Additionally, we aimed to correlate the apoptosis-related proteins expression profiles with SPP and clinical indexes. To this end, we employed antibody microarrays of the the apoptosis-related proteins in PBMCs from four RA patients and seven healthy controls. We used bioinformatics to screen several the apoptosis-related proteins. To validate key protein candidates, we performed Enzyme linked immunosorbent assay (ELISA) on 30 RA patients and 30 healthy controls. Results: We found the expression of ten the apoptosis-related proteins (caspase3, CD40, SMAC, HSP27, HTRA, IGFBP-1, IGFBP-6, sTNF-R1, sTNF-R2, TRAILR-3) were significantly altered in PBMCs of RA patients. Receiver operating characteristic (ROC) curve analysis suggested that these ten the apoptosis-related proteins are potential biomarkers of RA. Spearman Correlation analysis and Logistic-regression analysis revealed that the 10 selected the apoptosis-related proteins correlated with SPP and clinical indexes. Conclusion: Therefore, we highlight some the apoptosis-related proteins may serve as potential biomarkers in prediction of SPP for RA patients, although the underlying mechanisms need to be further explored.

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