title: MicroRNA-34c promotes osteoclast differentiation through targeting LGR4.
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.
authors.affiliation: Department of Orthopaedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Cong
authors.affiliation: Department of Dermatology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China. Electronic address: tian_xn2009@163.com.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Orthopaedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China.
authors.forename: Jinzhu
authors.initials: J
authors.lastname: Fan
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Orthopaedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Fu
mesh_terms: D024509:3' Flanking Region; D000818:Animals; D002454:Cell Differentiation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology*; D000067996:RAW 264.7 Cells; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: C496200:LGR4 protein, mouse; C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled
keywords: GSK3-β; LGR4; Osteoclast differentiation; Osteoporosis; miR-34c