1.Role of ceRNA network in inflammatory cells of rheumatoid arthritis.
Xiaoyu HE ; Haohua HE ; Yan ZHANG ; Tianyu WU ; Yongjie CHEN ; Chengzhi TANG ; Tian XIA ; Xiaonan ZHANG ; Changhao XIE
Journal of Central South University(Medical Sciences) 2023;48(5):750-759
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by inflammatory cells. Various inflammatory cells involved in RA include fibroblast-like synoviocytes, macrophages, CD4+T-lymphocytes, B lymphocytes, osteoclasts and chondrocytes. The close interaction between various inflammatory cells leads to imbalance of immune response and disorder of the expression of mRNA in inflammatory cells. It helps to drive production of pro-inflammatory cytokines and stimulate specific antigen-specific T- and B-lymphocytes to produce autoantibodies which is an important pathogenic factor for RA. Competing endogenous RNA (ceRNA) can regulate the expression of mRNA by competitively binding to miRNA. The related ceRNA network is a new regulatory mechanism for RNA interaction. It has been found to be involved in the regulation of abnormal biological processes such as proliferation, apoptosis, invasion and release of inflammatory factors of RA inflammatory cells. Understanding the ceRNA network in 6 kinds of RA common inflammatory cells provides a new idea for further elucidating the pathogenesis of RA, and provides a theoretical basis for the discovery of new biomarkers and effective therapeutic targets.
Humans
;
Arthritis, Rheumatoid/genetics*
;
MicroRNAs/metabolism*
;
Synoviocytes/pathology*
;
Cytokines/metabolism*
;
RNA, Messenger/metabolism*
;
Fibroblasts/pathology*
;
Cell Proliferation
2.Meta-Analysis of Genetic Association Studies.
Annals of Laboratory Medicine 2015;35(3):283-287
The object of this review is to help readers to understand meta-analysis of genetic association study. Genetic association studies are a powerful approach to identify susceptibility genes for common diseases. However, the results of these studies are not consistently reproducible. In order to overcome the limitations of individual studies, larger sample sizes or meta-analysis is required. Meta-analysis is a statistical tool for combining results of different studies on the same topic, thus increasing statistical strength and precision. Meta-analysis of genetic association studies combines the results from independent studies, explores the sources of heterogeneity, and identifies subgroups associated with the factor of interest. Meta-analysis of genetic association studies is an effective tool for garnering a greater understanding of complex diseases and potentially provides new insights into gene-disease associations.
Arthritis, Rheumatoid/genetics/pathology
;
Databases, Factual
;
*Genetic Association Studies
;
Genotype
;
Humans
;
Polymorphism, Single Nucleotide
;
Receptors, Immunologic/genetics
3.Lack of Relationship between Vitamin D Receptor Polymorphism and Bone Erosion in Rheumatoid Arthritis.
Chung Keun LEE ; Jeong Soo HONG ; You Sook CHO ; Bin YOO ; Ghi Su KIM ; Hee Boom MOON
Journal of Korean Medical Science 2001;16(2):188-192
We performed this study to investigate the possible association between vitamin D receptor (VDR) gene polymorphism and the focal bone erosion in rheumatoid arthritis (RA) patients in Korea. One hundred and fifty-seven RA patients were enrolled and two control groups were selected. The focal bone erosion score was assessed by modified Sharp's method. Genotyping of VDR polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis using two restriction enzyme Taq I and Bsm I. Notably, the distribution of VDR genotype in Korean population was different from Caucasians. The frequencies of "tt" and "BB" genotypes were very rare both in RA patients and in control groups. The frequency distribution of the Taq I and Bsm I genotype was not different between RA patients (TT, 93.6%; Tt, 6.4%; tt, 0%; BB, 0.6%; Bb, 5.1%; bb, 94.3%) and control groups (TT, 90.8%; Tt, 7.5%; tt, 1.7%; BB, 1.4%; Bb, 8.1%; bb, 90.5%). There was no significant difference in the focal bone erosion score (mean+/-SD) according to the VDR genotypes of RA patients (TT, 0.92+/-1.79; Tt, 0.4+/-0.79; Bb, 0.43+/-0.80; bb, 0.92+/-1.79; p>0.05). In conclusion, these results suggest that VDR gene polymorphisms are not associated with the focal bone erosion in RA patients in Korea.
Adolescence
;
Adult
;
Aged
;
Aged, 80 and over
;
Arthritis, Rheumatoid/*genetics/*pathology
;
Bone and Bones/*pathology
;
Female
;
Genotype
;
Human
;
Linkage Disequilibrium
;
Male
;
Middle Age
;
*Polymorphism (Genetics)
;
Receptors, Calcitriol/*genetics
4.Crosstalk between FLS and chondrocytes is regulated by HIF-2alpha-mediated cytokines in arthritis.
Yun Hyun HUH ; Gyuseok LEE ; Won Hyun SONG ; Jeong Tae KOH ; Je Hwang RYU
Experimental & Molecular Medicine 2015;47(12):e197-
Rheumatoid arthritis (RA) and osteoarthritis (OA), two common types of arthritis, affect the joints mainly by targeting the synovium and cartilage. Increasing evidence indicates that a significant network connects synovitis and cartilage destruction during the progression of arthritis. We recently demonstrated that hypoxia-inducible factor (HIF)-2alpha causes RA and OA by regulating the expression of catabolic factors in fibroblast-like synoviocytes (FLS) or chondrocytes. To address the reciprocal influences of HIF-2alpha on FLS and chondrocytes, we applied an in vitro co-culture system using a transwell apparatus. When co-cultured with HIF-2alpha-overexpressing chondrocytes, FLS exhibited increased expression of matrix metalloproteinases and inflammatory mediators, similar to the effects induced by tumor-necrosis factor (TNF)-alpha treatment of FLS. Moreover, chondrocytes co-cultured with HIF-2alpha-overexpressing FLS exhibited upregulation of Mmp3 and Mmp13, which is similar to the effects induced by interleukin (IL)-6 treatment of chondrocytes. We confirmed these differential HIF-2alpha-induced effects via distinct secretory mediators using Il6-knockout cells and a TNF-alpha-blocking antibody. The FLS-co-culture-induced gene expression changes in chondrocytes were significantly abrogated by IL-6 deficiency, whereas TNF-alpha neutralization blocked the alterations in gene expression associated with co-culture of FLS with chondrocytes. Our results further suggested that the observed changes might reflect the HIF-2alpha-induced upregulation of specific receptors for TNF-alpha (in FLS) and IL-6 (in chondrocytes). This study broadens our understanding of the possible regulatory mechanisms underlying the crosstalk between the synovium and cartilage in the presence of HIF-2alpha, and may suggest potential new anti-arthritis therapies.
Animals
;
Arthritis/genetics/*immunology/pathology
;
Arthritis, Rheumatoid/genetics/immunology/pathology
;
Basic Helix-Loop-Helix Transcription Factors/genetics/*immunology
;
Cells, Cultured
;
Chondrocytes/immunology/metabolism/*pathology
;
Coculture Techniques
;
Fibroblasts/immunology/metabolism/*pathology
;
Gene Expression Regulation
;
Interleukin-6/genetics/*immunology
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Osteoarthritis/genetics/immunology/pathology
;
Synovial Membrane/immunology/metabolism/*pathology
;
Tumor Necrosis Factor-alpha/genetics/*immunology
;
Up-Regulation
5.Effect of indomethacin on expression of interleukin-6 caused by lipopolysaccharide in rheumatoid arthritic patients' synoviocyte.
Jin-ye BAI ; Bai-he LIU ; Dan-yang ZHAO ; Gui-fang CHENG
Acta Pharmaceutica Sinica 2003;38(11):809-812
AIMTo study the effects of indomethacin on interleukin-6 (IL-6) expression stimulated with lipopolysaccharide (LPS) in rheumatoid arthritic patients' synoviocyte.
METHODSFibroblast-like cells (FLS) from rheumatoid arthritic patients' joint tissue were cultured for 24 h and incubated 24 h with LPS (1 mg.L-1) or the supernatant of U937 cells stimulated by LPS (1 mg.L-1). After indomethacin or dexamethasone added into the supernatant of U937 cells, FLS was incubated with the super natant for 24 h. The expression of IL-6 protein was detected by radioimmunoassay. The mRNA expression of IL-6 was accessed by RT-PCR.
RESULTSLPS did not obviously affect the growth of FLS, and the protein secretion and mRNA expression of IL-6 were not changed in FLS treated with LPS. The IL-6 secretion and IL-6 mRNA expression were significantly increased in FLS cultured with the supernatant from U937 cell treated with LPS. Indomethacin at concentrations of 1 x 10(-7)-1 x 10(-5) mol.L-1 obviously inhibited the protein secretion and mRNA expression of IL-6 in FLS cultured with the supernatant from U937 cell stimulated with LPS, and the inhibitory effects increased as the concentrations of indomethacin increased.
CONCLUSIONIndomethacin can inhibit the increase of IL-6 expression caused by supernatant of U937 cells stimulated with LPS in FLS.
Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Arthritis, Rheumatoid ; metabolism ; pathology ; Cells, Cultured ; Fibroblasts ; metabolism ; pathology ; Humans ; Indomethacin ; pharmacology ; Interleukin-6 ; biosynthesis ; genetics ; Lipopolysaccharides ; pharmacology ; RNA, Messenger ; genetics ; Synovial Membrane ; metabolism ; pathology ; U937 Cells
6.Expression of FLICE-inhibitory protein in synovial tissue and its association with synovial inflammation in juvenile idiopathic arthritis.
Feng-Xia WU ; Li-Jun WU ; Xiong-Yan LUO ; Ming-Hui YANG ; Zhong TANG ; Chuan-Mei XIE ; Jing-Guo ZHOU ; Jian-Long GUAN ; Guo-Hua YUAN
Chinese Medical Sciences Journal 2010;25(1):20-26
OBJECTIVETo examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation.
METHODSThe expression of FLIP was assessed in 11 JIA and 3 normal synovial tissue samples by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The cell types expressing FLIP were further characterized, and the correlation of FLIP expression with the degree of synovial inflammation, as well as the activity of caspase 8 was then analyzed.
RESULTSRT-PCR revealed the expression of FLIP mRNA in all 11 JIA samples, but not in 3 normal synovial tissues. In JIA, FLIP expression could be found in both the lining and sublining layers, mainly in the macrophage-like cells. Moreover, the expression of FLIP in JIA synovial tissues was positively correlated with the degree of synovial inflammation (r = 0.563, P < 0.05).
CONCLUSIONThe expression of antiapoptotic FLIP in JIA synovial tissue and its correlation to accumulation of inflammatory cells in synovial tissue suggests that FLIP potentially extends the lifespan of synovial cells and thus contributes to the progression of joint destruction.
Adolescent ; Arthritis, Juvenile ; metabolism ; pathology ; CASP8 and FADD-Like Apoptosis Regulating Protein ; genetics ; metabolism ; Caspase 8 ; metabolism ; Child ; Female ; Humans ; Inflammation ; metabolism ; pathology ; Male ; Protein Isoforms ; genetics ; metabolism ; Synovial Membrane ; cytology ; metabolism ; pathology
7.Effects of TNF-alpha receptor blocking peptide on adjuvant arthritis in rats.
Ya-ping HE ; Zhuo-ya LI ; Xiao-dan JIANG ; Wei FENG ; Yong XU ; Ping XIONG
Acta Pharmaceutica Sinica 2003;38(12):889-892
AIMTo study the effects of TNF receptor blocking peptide on adjuvant arthritis in rats.
METHODSThe model of rat adjuvant arthritis was induced by injection of complete Freund's adjuvant. The TNF receptor blocking peptide was injected locally in the ankle. The ankle swelling, the pathologic changes in the ankle joint and the expression of IL-1 beta mRNA and TNF-alpha mRNA by peritoneal macrophages (RT-PCR) were observed.
RESULTSThe model of rat adjuvant arthritis induced by injection of complete Freund's adjuvant was similar to human rheumatoid arthritis. The treatment with TNF receptor blocking peptide for 10 days resulted in complete inhibition of joint swelling, a decrease in infiltration of inflammatory cell into joint tissue, an obvious alleviation of inflammatory pathological damages and an apparent decline of TNF-alpha mRNA and IL-1 beta mRNA of peritoneal macrophages of rats.
CONCLUSIONThe TNF receptor blocking peptide can protect the joint from inflammatory damage induced by adjuvant arthritis by suppression of TNF-alpha and IL-1 production, thereby alleviating the pathological injury of joint and controlling effectively the clinic course of arthritis.
Animals ; Ankle Joint ; pathology ; Arthritis, Experimental ; immunology ; pathology ; Interleukin-1 ; biosynthesis ; genetics ; Macrophages, Peritoneal ; metabolism ; Male ; Peptides ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Receptors, Tumor Necrosis Factor ; antagonists & inhibitors ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics
8.Two Likely Pathogenic Variants of COL2A1 in Unrelated Korean Patients With Ocular-Only Variants of Stickler Syndrome: The First Molecular Diagnosis in Korea.
Je Moon YOON ; Mi Ae JANG ; Chang Seok KI ; Sang Jin KIM
Annals of Laboratory Medicine 2016;36(2):166-169
Stickler syndrome is a genetically heterogeneous disorder that affects the ocular, auditory, and musculoskeletal systems. Ocular-only variant of Stickler syndrome type 1 (OSTL1) is characterized by high risk of retinal detachment without systemic involvement and is caused by alternatively spliced exon 2 mutation of COL2A1. We report the cases of two Korean families with OSTL1 carrying likely pathogenic variants of COL2A1. All patients presented with membranous vitreous anomaly, peripheral retinal degeneration, and/or rhegmatogenous retinal detachment, but no systemic manifestations. By genetic analysis, two likely pathogenic non-exon 2 variants, c.2678dupC (p.Ala895Serfs*49) and c.3327+ 1G>C, were identified in COL2A1. Our results demonstrate that COL2A1 defects in OSTL1 are not confined to mutations in exon 2. Together with molecular data, ophthalmologists should consider genetic diagnosis of Stickler syndrome in patients with vitreous anomaly to prevent blindness from retinal detachment. To our knowledge, this is the first report of genetically confirmed OSTL1 in Korea.
Adult
;
Arthritis/*genetics/pathology
;
Asian Continental Ancestry Group/*genetics
;
Base Sequence
;
Collagen Type II/*genetics
;
Connective Tissue Diseases/*genetics/pathology
;
DNA Mutational Analysis
;
Exons
;
Female
;
Hearing Loss, Sensorineural/*genetics/pathology
;
Humans
;
Male
;
Middle Aged
;
Republic of Korea
;
Retinal Detachment/*genetics/pathology
;
Visual Acuity
9.Effect of Yangqixue Qufengshi Recipe on rheumatoid arthritis model mice under different genetic backgrounds.
Fen LI ; Hong WU ; Jun-wei DENG ; Song-qing FAN ; Jing TIAN ; Jie-sheng GAO ; Ya-hui ZHU ; Guang-xiu LU
Chinese journal of integrative medicine 2006;12(1):46-49
OBJECTIVETo study the effect of Yangqixue Qufengshi Recipe (YQXQFS) on rheumatoid arthritis (RA) model mice under different genetic backgrounds.
METHODSCollagen Induced Arthritis (CIA) were established on HLA-DR4 transgenic (TG) mice and non-transgenic (NTG) mice, which partly were raised with YQXQFS, and the onset day of CIA, the level of type II collagen (CII)-reactive antibodies and the pathological scores of CIA were assessed.
RESULTSUnder HLA-DR4 TG background (compared with NTG mice), the earlier onset day of CIA (11.22 +/- 3.35 days vs 16.56 +/- 4.75 days, P < 0.05) and higher level of CII-reactive antibodies (0.2274 +/- 0.1390 microg/ml vs 0.1101 +/- 0.0560 microg/ml, P < 0.05) were observed, but the pathological scores of CIA remained unchanged. YQXQFS could not influence the onset day of CIA and the level of CII-reactive antibodies, but had a certain effect on the total pathological scores (6.56 +/- 3.43 scores vs 11.11 +/- 5.64 scores) and bone erosion (0.22 +/- 0.44 scores vs 1.67 +/- 1.50 scores) of CIA on NTG mice (P < 0.05), NTG YQXQFS group compared with NTG experimental group.
CONCLUSIONYQXQFS had a certain effect on RA model, but had no significant effect on HLA-DR4 related CIA.
Animals ; Antibodies ; blood ; Antirheumatic Agents ; therapeutic use ; Arthritis, Experimental ; drug therapy ; Arthritis, Rheumatoid ; drug therapy ; immunology ; pathology ; Collagen Type II ; immunology ; Drugs, Chinese Herbal ; therapeutic use ; HLA-DR4 Antigen ; genetics ; Mice ; Mice, Inbred Strains ; Mice, Knockout
10.Moxibustion regulates T-regulatory/T-helper 17 cell balance by modulating the microRNA-221/suppressor of cytokine signaling 3 axis in a mouse model of rheumatoid arthritis.
Chuang ZHAO ; Xiao-Yan LI ; Zun-Yuan LI ; Miao LI ; Zhi-Dan LIU
Journal of Integrative Medicine 2022;20(5):453-462
OBJECTIVE:
Rheumatoid arthritis (RA) progression is associated with the balance of T-regulatory (Treg) and T-helper 17 (Th17) cells, while the role of microRNAs (miRs) in regulating Treg/Th17 cell balance has not been clarified. This study aimed to assess whether moxibustion could regulate Treg/Th17 cell balance by modulating the miR-221/suppressor of cytokine signaling 3 (SOCS3) axis in the RA mouse model.
METHODS:
A mouse model of collagen-induced arthritis (CIA) was established in male DBA/1J mice. Twenty-two days after CIA induction, the mice received daily treatment with moxibustion for 12 times. Pathological scores were assessed according to the levels of synovial hyperplasia. The expression levels of cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-17 and IL-10 were analyzed in serum by enzyme-linked immunosorbent assay. The cluster of differentiation 4 (CD4+) splenocytes was analyzed by fluorescence-activated cell sorting. The expression levels of RA-related miRs and target genes were subsequently detected, and the target of miR-221 was confirmed by the dual-luciferase reporter assay.
RESULTS:
It was revealed that moxibustion treatment decreased the pathological scores and downregulated the expression levels of IL-1β, IL-6, TNF-α, IFN-γ and IL-17, while upregulated the expression level of IL-10. The Treg/Th17 cell balance was regulated by moxibustion treatment. The expression level of miR-221 was suppressed by moxibustion treatment. Furthermore, SOCS3 was found as the direct target of miR-221, which mediated the function of moxibustion by regulating the Treg/Th17 cell balance.
CONCLUSION
Moxibustion therapy regulated the Treg/Th17 cell balance by modulating the miR-221/SOCS3 axis in the RA mouse model.
Animals
;
Arthritis, Experimental/therapy*
;
Arthritis, Rheumatoid/therapy*
;
Cytokines
;
Disease Models, Animal
;
Interleukin-10
;
Interleukin-17
;
Interleukin-6
;
Male
;
Mice
;
Mice, Inbred DBA
;
MicroRNAs/genetics*
;
Moxibustion
;
T-Lymphocytes, Regulatory
;
Th17 Cells/pathology*
;
Tumor Necrosis Factor-alpha