title: MicroRNA-9 regulates osteoblast differentiation and angiogenesis via the AMPK signaling pathway.
abstract: MiR-9 has been found to be involved in the repair of spinal cord injury and regulates the proliferation and differentiation of mesenchymal stem cells. However, the role of miR-9 in repair of bone defects has not been well studied. The current study was designed to investigate its role and potential underlying mechanism in regulating osteoblast differentiation and angiogenesis. After treating the murine pre-osteoblast cell line MC3T3-E1 with BMP2, miR-9 expression was obviously down-regulated. Following transfection with miR-9 mimics, its overexpression enhanced the differentiation of MC3T3-E1 cells into osteoblasts as evidence that miR-9 up-regulated the mRNA levels of osteoblast differentiation-related protein, as well as increased differentiation and mineralization of osteoblasts. Further functional analysis has shown that miR-9 overexpression effectively increased human umbilical vein endothelial cell proliferation. Moreover, miR-9 up-regulation promoted cell migration, VEGF, and VE-cadherin concentrations, as well as tube formation in vitro. The mechanistic assay demonstrated that overexpression of miR-9-induced activation of the AMPK signaling pathway. Taken together, our findings suggested that miR-9 overexpression promoted osteoblast differentiation and angiogenesis via the AMPK signaling pathway, representing a novel and potential therapeutic target for the treatment of bone injury-related diseases.
authors.affiliation: Department of Pediatric Orthopedics, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China. qujining@yeah.net.
authors.forename: Jining
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Trauma, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China.
authors.forename: Daigang
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Emergency, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China. 13772120089@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pediatric Orthopedics, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China.
authors.forename: Wusheng
authors.initials: W
authors.lastname: Miao
authors.affiliation: Department of Pediatric Orthopedics, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Pediatric Orthopedics, Honghui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, 710054, China.
authors.forename: Meifen
authors.initials: M
authors.lastname: Zhou
mesh_terms: D016475:3T3 Cells; D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D061307:Human Umbilical Vein Endothelial Cells; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D000263:Adenylate Kinase
keywords: AMPK; Angiogenesis; Bone repair; MicroRNA-9; Osteoblast differentiation