Functional role of PPAR-γ on the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis

Li, Xiaofeng; Sun, Ying‐Yin; Bao, Jing; Chen, Xin; Li, Yuhuan; Yang, Yang; Zhang, Lei; Huang, Cheng; Wu, Boxi; Meng, Xiao‐Ming; Li, Jun

doi:10.1038/s41598-017-12570-6

Cited by 51 publications

(54 citation statements)

References 37 publications

(39 reference statements)

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“…PPARG, a known inhibitor of TNFSF11-mediated osteoclastogenesis, was downregulated in the ODP network. This result agrees with the findings of Li et al (2017) . The upregulation of CD27 receptor is in accordance with the reports of high levels of CD27 in the synovial tissue of RA patients ( Tak et al, 1996 ).…”

Section: Discussionsupporting

confidence: 94%

“…In addition to STAT and AP1 proteins, the other DNA binding core protein peroxisome proliferator activated receptor gamma (PPARG) was observed to be downregulated which is in agreement with the results of Li et al (2017) . The attachment of the shell network resulted in the inclusion of nine differentially regulated DNA-binding proteins in the directed ODP network.…”

Section: Resultssupporting

confidence: 86%

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Effects of rheumatoid arthritis associated transcriptional changes on osteoclast differentiation network in the synovium

Harshan

Dey

Ragunathan

2018

PeerJ

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BackgroundOsteoclast differentiation in the inflamed synovium of rheumatoid arthritis (RA) affected joints leads to the formation of bone lesions. Reconstruction and analysis of protein interaction networks underlying specific disease phenotypes are essential for designing therapeutic interventions. In this study, we have created a network that captures signal flow leading to osteoclast differentiation. Based on transcriptome analysis, we have indicated the potential mechanisms responsible for the phenotype in the RA affected synovium.MethodWe collected information on gene expression, pathways and protein interactions related to RA from literature and databases namely Gene Expression Omnibus, Kyoto Encyclopedia of Genes and Genomes pathway and STRING. Based on these information, we created a network for the differentiation of osteoclasts. We identified the differentially regulated network genes and reported the signaling that are responsible for the process in the RA affected synovium.ResultOur network reveals the mechanisms underlying the activation of the neutrophil cytosolic factor complex in connection to osteoclastogenesis in RA. Additionally, the study reports the predominance of the canonical pathway of NF-κB activation in the diseased synovium. The network also confirms that the upregulation of T cell receptor signaling and downregulation of transforming growth factor beta signaling pathway favor osteoclastogenesis in RA. To the best of our knowledge, this is the first comprehensive protein–protein interaction network describing RA driven osteoclastogenesis in the synovium.DiscussionThis study provides information that can be used to build models of the signal flow involved in the process of osteoclast differentiation. The models can further be used to design therapies to ameliorate bone destruction in the RA affected joints.

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Section: Discussionsupporting

confidence: 94%

Section: Resultssupporting

confidence: 86%

Effects of rheumatoid arthritis associated transcriptional changes on osteoclast differentiation network in the synovium

Harshan

Dey

Ragunathan

2018

PeerJ

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“…At the same time, the inhibition of PSMA1 also significantly reduced the expression of PPARγ. Combined with the biological effects of Pref-1 and PPARγ, this is consistent with some studies that show that PSMA1 potentially regulates the c-Myc signaling pathway (Kulichkova et al, 2010;Li et al, 2017b), Notch3 (Ogura et al, 2003;Zhang et al, 2007), and Pde3b (Hopitzan et al, A and C show the lipid deposition in the adipocytes of negative control (NC) group and PSMA1-siRNA group under the microscope (200 X), respectively; B and D are the enlarged image of selected area from A and C, respectively; E is the relative triglyceride content level in the NC and PSMA1-siRNA groups. Differential relative triglyceride content obtained from NC and PSMA1-siRNA groups were compared by the t test.…”

Section: Discussionsupporting

confidence: 89%

Effects of PSMA1 on the differentiation and lipid deposition of bovine preadipocytes

Chen

Jiang

et al. 2019

R. Bras. Zootec.

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Breeding and genetics Full-length research article Effects of PSMA1 on the differentiation and lipid deposition of bovine preadipocytes ABSTRACT-In this study, our goal was to clarify the role of proteasomal subunit α-1 (PSMA1) in both the differentiation of preadipocytes and the accumulation of lipids in adipocytes. Preadipocytes from healthy one-day-old calves were collected, isolated, and cultured in vitro. The expression pattern of the PSMA1 gene was explored during the differentiation of bovine preadipocytes firstly. Then, the expression of the PSMA1 gene was inhibited by transfection of a chemically synthesized small interfering RNA (siRNA) before differentiation. After induction of differentiation, the mRNA levels of key regulating genes involved in preadipocyte differentiation and the lipid content of mature adipocytes with and without inhibition of PSMA1 were detected by qRT-PCR and oil red O staining, respectively. The data showed that PSMA1 mRNA was differentially expressed during the differentiation of bovine preadipocytes under normal culture conditions in vitro. The expression level of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT enhancer-binding protein alpha (C/EBPα), and lipoprotein lipase (LPL) were significantly decreased in the transfected PSMA1-siRNA group compared with those in the control group, and the mRNA levels of the preadipocyte factor-1 (Pref-1) were significantly upregulated in the transfected PSMA1-siRNA group compared with those in the control group. In addition, significantly fewer lipid droplets were formed by adipocytes transfected with PSMA1-siRNA than by the negative control group (adipocytes transfected with NC-siRNA). Therefore, PSMA1 plays an important role in differentiation and lipid deposition.

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“…Its capabilities include: chemokine ampli cation, endothelial cell activation, leukocyte accumulation [27] , experiencing cardiovascular comorbidity [28] , acceleration destruction of osteoclast and chondrocyte, and demonstrating metabolic syndrome [29] . Related studies have reported that PPAR-γ may additionally induce activation Wnt/β-catenin signaling [30] .…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes and signaling pathways in rheumatoid arthritis by integrated bioinformatics analysis

Zhou

Chen

et al. 2020

Preprint

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Abstract Background The disability rate associated with rheumatoid arthritis (RA) ranks high among inflammatory joint diseases. However, the cause and potential molecular events are as yet not clear. Here, we aimed to identify key genes and pathways involved in RA utilizing integrated bioinformatics analysis and uncover underlying molecular mechanisms. Materials and methods The expression profiles of GSE55235, GSE55457, GSE55584 and GSE77298 were downloaded from the Gene Expression Omnibus database, which contained 76 synovial membrane samples, including 49 RA samples and 27 controls. The microarray datasets were consolidated and differentially expressed genes (DEGs) were acquired and further analyzed by bioinformatics techniques. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using R (version 3.6.1), respectively. The protein-protein interaction (PPI) networks of DEGs were developed utilizing the STRING database. Results A total of 828 DEGs were recognized, with 758 up-regulated and 70 down-regulated. GO and KEGG pathway analyses demonstrated that these DEGs focused primarily on multifactorial binding, transcription activity, cytokin-cytokin receptor interaction and relevant signaling pathways. The 30 most firmly related genes among DEGs were identified from the PPI network. Conclusion This study shows that screening for DEGs and pathways utilizing integrated bioinformatics analyses could aid in the comprehension of the molecular mechanisms involved in RA development. In addition, our study provides valuable data for the effective prevention, diagnosis, treatment and rehabilitation of RA patients as well as providing potential targets for the treatment of RA.

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Functional role of PPAR-γ on the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis

Cited by 51 publications

References 37 publications

Effects of rheumatoid arthritis associated transcriptional changes on osteoclast differentiation network in the synovium

Effects of rheumatoid arthritis associated transcriptional changes on osteoclast differentiation network in the synovium

Effects of PSMA1 on the differentiation and lipid deposition of bovine preadipocytes

Identification of differentially expressed genes and signaling pathways in rheumatoid arthritis by integrated bioinformatics analysis

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