Roles of MicroRNAs in Bone Destruction of Rheumatoid Arthritis

Zhao, Hanxiao; Lu, Aiping; He, Xiaojuan

doi:10.3389/fcell.2020.600867

Cited by 17 publications

(9 citation statements)

References 100 publications

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“…RA pathogenesis is complex but the main pathologic features are synoviocyte proliferation and destruction of cartilage and bone. Collectively, these processes can cause a significant amount of pain and affect the quality of life adversely [ 12 ]. Joint symptoms can be divided into two types: synovial inflammation and destruction of joint structure.…”

Section: Discussionmentioning

confidence: 99%

An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis

et al. 2021

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Background Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease dominated by synovial hyperplasia and bone destruction. The male flower of Eucommia ulmoides Oliv. (EF) has been shown to exert effects on the inflammation caused by RA. However, how EF affects synoviocyte apoptosis and bone destruction on RA have not been investigated thoroughly. The effects of EF on apoptosis of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells, osteoclast differentiation of RAW264.7 cells, and bone destruction in a collagen-induced arthritis (CIA) model in rats were explored. Methods First, the main components of EF were identified by high-performance liquid chromatography. In vitro, we investigated the anti-proliferative and pro-apoptotic effects of EF on HFLS-RA cells by immunofluorescence assays, flow cytometry, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting; we also investigated how EF influenced the differentiation of RAW264.7 cells into osteoclasts. In vivo, we used a rat model of CIA to investigate the effects of EF on anti-arthritis activity, toe swelling, Arthritis Score, serum levels of metabolic bone factors, and pathologic conditions. Micro-computed tomography was used to scan ankle joints. mRNA and protein expression of factors related to the nuclear factor-kappa B (NF-κB) pathway were determined by RT-qPCR and western blotting, respectively. Results EF inhibited synoviocyte proliferation and promoted apoptosis in a dose-dependent manner. EF inhibited osteoclast differentiation by inhibiting activation of the NF-κB pathway. EF reduced articular inflammation in CIA rats, inhibited the expression of pro-angiogenic factors, and delayed the destruction of articular cartilage and bone. Our data indicated that EF acted via a mechanism related to bone metabolism induced by the NF-κB pathway. Conclusions EF exerts a potential therapeutic effect upon RA. Our research will help to elucidate the potential pharmacologic mechanisms associated with the beneficial effects of EF, and provide an experimental basis for EF application in clinical treatments. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis

et al. 2021

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“…showed that genes in the lncRNA-mRNA interaction network were enriched for terms related to production and function of miRNAs, which play important role in bone destruction of rheumatoid arthritis (Zhao et al, 2020), indicating that DE lncRNAs may also function by regulating miRNAs to influence the expression of targeted mRNAs.…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with previous reports indicating FoxO1 in SPAHO syndrome ( Berthelot et al, 2018 ), another nine genes including FoxO3 in the FoxO signaling pathway was also found to be regulated by DE lncRNAs in the SAPHO group. GO analysis showed that genes in the lncRNA-mRNA interaction network were enriched for terms related to production and function of miRNAs, which play important role in bone destruction of rheumatoid arthritis ( Zhao et al, 2020 ), indicating that DE lncRNAs may also function by regulating miRNAs to influence the expression of targeted mRNAs.…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis of lncRNA-mRNA Profile Reveals Potential Predictors for SAPHO Syndrome

Sun

et al. 2021

Front. Genet.

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Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is known as a rare disease characterized by inflammatory lesions on bones and skin. Polymorphism of clinical manifestation and lack of molecular biomarkers have both limited its diagnosis. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of long noncoding RNA (lncRNA)-messenger RNA (mRNA) profile in patients with SAPHO syndrome and healthy controls. A total of 4,419 differentially expressed (DE) mRNAs and 2,713 lncRNAs were identified (p < 0.05, fold change > 2) and a coexpression network was constructed to further investigate their regulatory interactions. The DE lncRNAs were predicted to interact with mRNAs in both cis and trans manners. Functional prediction found that the lncRNA-targeted genes may function in SAPHO syndrome by participating in biological process such as adipocytokine signaling pathway, ErbB signaling pathway, FoxO signaling pathway, as well as production and function of miRNAs. The expression levels of three pairs of coexpressed lncRNA-mRNAs were validated by qRT-PCR, and their relative expression levels were consistent with the RNA-seq data. The deregulated RNAs GAS7 and lnc-CLLU1.1-1:2 may serve as potential diagnostic biomarkers, and the combined receiver operating characteristic (ROC) curve of the two showed more reliable diagnostic ability with an AUC value of 0.871 in distinguishing SAPHO patients from healthy controls. In conclusion, this study provides a first insight into long noncoding RNA transcriptome profile changes associated with SAPHO syndrome and inspiration for further investigation on clinical biomarkers and molecular regulators of this inadequately understood clinical entity.

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“…The pathogenesis of RA is complex; the main pathological features are synovial cell proliferation and the destruction of cartilage and bone. Collectively, these processes can cause a significant amount of pain and can adversely affect the quality of life [12]. Joint symptoms can be divided into two types: synovial inflammation and joint structure destruction.…”

Section: Discussionmentioning

confidence: 99%

An Alcohol Extract Prepared From the Male Flower of Eucommia Ulmoides Oliv. Promotes Synovial Cell Apoptosis, Inhibits Osteoclast Differentiation and Ameliorates Bone Destruction in Rheumatoid Arthritis

Zhang

Wang

Chen

et al. 2021

Preprint

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Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with a complex pathogenesis and is dominated by synovial hyperplasia and bone destruction. Previous research has shown that the male flower of Eucommia ulmoides Oliv. (EF) can exert effect on the inflammation caused by rheumatoid arthritis. However, the effect of EF on synovial cell apoptosis and bone destruction on RA have yet to be investigated. In this study, the effects of the synovial cell apoptosis of the male flower of Eucommia ulmoides Oliv.(EF) on human fibroblast-like synoviocyte -RA (HFLS-RA) cells, the osteoclast differentiation of EF on RAW264.7 cells and the bone destruction of effects of EF on collagen-induced arthritis (CIA) rats were explored.Materials and methods: In vitro, we investigated the anti-proliferative and pro-apoptotic effects of EF on HFLS-RA cells by immunofluorescence assays, flow cytometry, RT-qPCR (Real-time quantitative polymerase chain reaction), and western blotting. We investigated the differentiation into osteoclasts effects of EF on RAW264.7 cells by the TRAP staining and western blotting. In vivo, we used a rat model of collagen-induced arthritis (CIA) to investigate the relative effects of EF on anti-arthritis activity, the toe swelling arthritis score, the serum levels of metabolic bone factors, and pathological conditions. Micro-computed tomography (micro-CT) was used to scan ankle joints while the mRNA and protein levels of factors related to the NF-κB pathway were determined by RT-qPCR and western blotting, respectively. Finally, the main chemical components of EF were identified by HPLC (High Performance Liquid Chromatography). Results: EF inhibited the proliferation of synovial cells and promoted apoptosis in a dose-dependent manner, inhibited the differentiation of osteoclast by inhibiting activation of the NF-κB pathway. We also found that EF reduced articular inflammation in CIA rats, inhibited the expression of pro-angiogenic factors, and delayed the destruction of articular cartilage and bone. Our data indicate that EF acts via a mechanism related to bone metabolism that is induced by the NF-κB pathway. Conclusions: Our findings indicate that EF exerts a potential therapeutic effect on rheumatoid arthritis. Our research will help to elucidate the potential pharmacological mechanisms associated with the beneficial effects of EF and provide an experimental basis for the application of EF in future clinical treatments.

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Roles of MicroRNAs in Bone Destruction of Rheumatoid Arthritis

Cited by 17 publications

References 100 publications

An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis

An alcohol extract prepared from the male flower of Eucommia ulmoides Oliv. promotes synoviocyte apoptosis and ameliorates bone destruction in rheumatoid arthritis

Integrative Analysis of lncRNA-mRNA Profile Reveals Potential Predictors for SAPHO Syndrome

An Alcohol Extract Prepared From the Male Flower of Eucommia Ulmoides Oliv. Promotes Synovial Cell Apoptosis, Inhibits Osteoclast Differentiation and Ameliorates Bone Destruction in Rheumatoid Arthritis

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