MicroRNA-124 inhibits the progression of adjuvant-induced arthritis in rats

Nakamachi, Yuji; Ohnuma, Kenichiro; Uto, Kenichi; Noguchi, Yoriko; Saegusa, Jun; Kawano, Seiji

doi:10.1136/annrheumdis-2014-206417

Cited by 80 publications

(62 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, Lee et al discovered that miR-124 inhibits osteoclastogenesis via NFATc [30,31]. However, much uncertainty still exists about the relation between miR-124 and osteoclastogenesis.…”

Section: Discussionmentioning

confidence: 99%

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

Tang¹,

Yin²,

Liu³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: With the aging population increases, senile osteoporosis has become a global public health problem. Previous evidence has shown that miR-124 has important effects on the occurrence and development of osteoporosis. However, the role of miR-124 in the process of osteoclastogenesis is still obscure. Methods: First of all, we measured the expression level of miR-124 in bone marrow monocytes (BMMs) of osteoporotic mice (ovariectomized mice: OVX). Next, we evaluated the alteration of miR-124 during osteoclast differentiation of BMMs. Then, BMMs were transfected with miR-124 mimics or inhibitors to explore the influences of miR-124 on osteoclast differentiation of BMMs in vitro. Furthermore, bioinformatics analysis and luciferase reporter assay were performed for prediction and identification of the target of miR-124. Results: BMMs from OVX mice exhibited lower expression of miR-124 compared with Sham mice. Additionally, miR-124 was down-regulated when BMMs differentiated into osteoclasts. In addition, inhibition of miR-124 promoted BMMs differentiated into osteoclasts in vitro, whereas overexpression of miR-124 attenuated this procedure, demonstrated by increased expression of osteoclast specific genes and TRAP staining. Furthermore, Rab27a was confirmed to be the direct target of miR-124 by bioinformatics, Western blot and luciferase reporter assay analysis. Conclusion: Our findings revealed that miR-124 has an important role in osteoclastogenesis via targeting Rab27a. Thus, targeting miR-124 promises a therapeutic potential in the treatment of osteoporosis.

show abstract

Section: Discussionmentioning

confidence: 99%

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

Tang¹,

Yin²,

Liu³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…miRNA-dependent mechanisms can turn off genes that promote monocyte differentiation to instead promote the differentiation of monocytes to mature, bone-resorbing osteoclasts [87]. Interestingly, it has been shown that treatment of rats with antigen-induced arthritis with miR-124 not only suppressed measures of inflammation, but also targeted critical mRNAs involved in osteoclastogenesis, including NFATc1 [88]. Further elucidation of bone-related pathways regulated by miRNAs in rheumatic diseases may provide new insights into pathogenesis, as well as new targets for therapy.…”

Section: Bone Resorption In Ramentioning

confidence: 99%

Bone as a Target Organ in Rheumatic Disease: Impact on Osteoclasts and Osteoblasts

Baum

Gravallese

2015

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

Dysregulated bone remodeling occurs when there is an imbalance between bone resorption and bone formation. In rheumatic diseases, including rheumatoid arthritis (RA) and seronegative spondyloarthritis, systemic and local factors disrupt the process of physiologic bone remodeling. Depending upon the local microenvironment, cell types, and local mechanical forces, inflammation results in very different effects on bone, promoting bone loss in the joints and in periarticular and systemic bone in RA and driving bone formation at enthesial and periosteal sites in diseases such as ankylosing spondylitis (AS), included within the classification of axial spondyloarthritis. There has been a great deal of interest in the role of osteoclasts in these processes and much has been learned over the past decade about osteoclast differentiation and function. It is now appreciated that osteoblast-mediated bone formation is also inhibited in the RA joint, limiting the repair of erosions. In contrast, osteoblasts function to produce new bone in AS. The Wnt and BMP signaling pathways have emerged as critical in the regulation of osteoblast function and the outcome for bone in rheumatic diseases, and these pathways have been implicated in both bone loss in RA and bone formation in AS. These pathways provide potential novel approaches for therapeutic intervention in diseases in which inflammation impacts bone.

show abstract

“…In osteoclasts, miR-124 can target NFATc1, key transcription factor; it also reduces osteoclast precursor proliferation and motility by targeting integrin B1 (ITGB1), RhoA and Rac1 [97]. In a rat inflammatory arthritis model, miR-124 mimic injection was shown to ameliorate progression of the arthritic lesion by decreasing osteoclast formation [100]. …”

Section: Mir-snps: Snps In Mirna Genes Altering Their Biogenesis Amentioning

confidence: 99%

MicroRNA variants as genetic determinants of bone mass

Dole

Delany

2016

Bone

View full text Add to dashboard Cite

Single nucleotide polymorphisms (SNPs) are the most abundant genetic variants that contribute to the heritability of bone mass. MicroRNAs (miRNAs, miRs) are key post-transcriptional regulators that modulate the differentiation and function of skeletal cells by targeting multiple genes in same or distinct signaling pathways. SNPs in miRNA genes and miRNA binding sites can alter miRNA abundance and mRNA targeting. This review describes the potential impact of miRNA-related SNPs on skeletal phenotype. Although many associations between SNPs and bone mass have been described, this review is limited to gene variants for which a function has been experimentally validated. SNPs in miRNA genes (miR-SNPs) that impair miRNA processing and alter the abundance of mature miRNA are discussed for miR-146a, miR-125a, miR-196a, miR-149 and miR-27a. SNPs in miRNA targeting sites (miR-TS-SNPs) that alter miRNA binding are described for the bone remodeling genes bone morphogenetic protein receptor 1 (Bmpr1), fibroblast growth factor 2 (Fgf2), osteonectin (Sparc) and histone deacetylase 5 (Hdac5). The review highlights two aspects of miRNA-associated SNPs: the mechanism for altering miRNA mediated gene regulation, and the potential of miR-associated SNPs to alter osteoblast, osteoclast or chondrocyte differentiation and function. Given the polygenic nature of skeletal diseases like osteoporosis and osteoarthritis, validating the function of additional miRNA-associated SNPs has the potential to enhance our understanding of the genetic determinants of bone mass and predisposition to selected skeletal diseases.

show abstract

MicroRNA-124 inhibits the progression of adjuvant-induced arthritis in rats

Abstract: We found that miR-124 ameliorated AIA by suppressing critical prerequisites for arthritis development, such as RANKL and NFATc1. Thus, miR-124a is a candidate for therapeutic use for human rheumatoid arthritis.

Cited by 80 publications

References 40 publications

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

Bone as a Target Organ in Rheumatic Disease: Impact on Osteoclasts and Osteoblasts

MicroRNA variants as genetic determinants of bone mass

Contact Info

Product

Resources

About