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MicroRNA-34c promotes osteoclast differentiation through targeting LGR4
- Source :
- Gene. 610:1-8
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- MicroRNAs have emerged as important regulators of osteoclast differentiation in recent years. Of these, miR-34c has been reported to play an important role in bone development. However, its role and the underlying mechanism in osteoclast differentiation remains poorly understood. In this study, we aimed to investigate the precise role and molecular mechanism of miR-34c in osteoclast differentiation. We found an obvious increase in miR-34c expression during osteoclast differentiation in osteoclast precursors induced by receptor activator of nuclear factor κB (NF-κB) ligand and macrophage colony-stimulating factor in vitro. Further experiments showed that overexpression of miR-34c significantly promoted osteoclast differentiation while suppression of miR-34c showed the opposite effect. Interestingly, bioinformatics analysis and dual-luciferase reporter assays showed that miR-34c targets the 3'-untranslated region of leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4). The expression of LGR4 was regulated by miR-34c in osteoclasts. Moreover, miR-34c regulated NF-κB and glycogen synthase kinase 3-β signaling during osteoclast differentiation. Overexpression of LGR4 partially reversed the promoting effect of miR-34c overexpression on osteoclast differentiation. Taken together, our study suggests that miR-34c contributes to osteoclast differentiation by targeting LGR4, providing novel insights into understanding the molecular mechanism underlying osteoclast differentiation.
- Subjects :
- Male
musculoskeletal diseases
0301 basic medicine
medicine.medical_specialty
Osteoclasts
Receptors, G-Protein-Coupled
Mice
03 medical and health sciences
chemistry.chemical_compound
Osteoclast
GSK-3
Internal medicine
microRNA
Genetics
medicine
Animals
3' Flanking Region
Receptor
biology
Activator (genetics)
NF-kappa B
Cell Differentiation
NF-κB
General Medicine
In vitro
Cell biology
Mice, Inbred C57BL
MicroRNAs
RAW 264.7 Cells
030104 developmental biology
Endocrinology
medicine.anatomical_structure
chemistry
RANKL
biology.protein
Subjects
Details
- ISSN :
- 03781119
- Volume :
- 610
- Database :
- OpenAIRE
- Journal :
- Gene
- Accession number :
- edsair.doi.dedup.....0acbd6ab66b8df02b450f499956e5a3d