title: microRNA-21 mediates stretch-induced osteogenic differentiation in human periodontal ligament stem cells.
abstract: microRNAs (miRNAs) are short 20- to 22-nucleotide noncoding RNAs that negatively regulate the expression of target genes at the post-transcriptional level. The expression of specific miRNAs and their roles in the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) exposed to mechanical stretch remain unclear. Here, we found that stretch induced both osteogenic differentiation and the differential expression of miR-21 in PDLSCs. Furthermore, we identified activin receptor type IIB (ACVR2B) as a target gene of miR-21. Luciferase reporter assays showed that miR-21 interacts directly with the 3'-untranslated repeat sequence of ACVR2B mRNA. Mechanical stretch suppressed ACVR2B protein levels in PDLSCs, and this suppressive effect was modulated when endogenous miR-21 levels were either enhanced or inhibited. Both stretch and the expression of miR-21 altered endogenous ACVR2B protein levels and thus the osteogenic differentiation of PDLSCs. In addition, gain- and loss of function of ACVR2B mediated the osteogenic differentiation of PDLSCs. This study demonstrates that miR-21 is a mechanosensitive gene that plays an important role in the osteogenic differentiation of PDLSCs exposed to stretch.
authors.affiliation: 1 Department of Orthodontics, Shandong Provincial Key Laboratory of Oral Biomedicine, School of Stomatology, Shandong University , Jinan, People's Republic of China .
authors.forename: Fulan
authors.initials: F
authors.lastname: Wei
authors.forename: Dongxu
authors.initials: D
authors.lastname: Liu
authors.forename: Cheng
authors.initials: C
authors.lastname: Feng
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Shuangyan
authors.initials: S
authors.lastname: Yang
authors.forename: Yijun
authors.initials: Y
authors.lastname: Hu
authors.forename: Gang
authors.initials: G
authors.lastname: Ding
authors.forename: Songlin
authors.initials: S
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D030301:Activin Receptors, Type II / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000293:Adolescent; D016723:Bone Remodeling / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D005822:Genetic Vectors; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D010513:Periodontal Ligament / Q000166:cytology*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C039919:RNA, recombinant; D016212:Transforming Growth Factor beta; D012313:RNA; C579679:ACVR2B protein, human; D030301:Activin Receptors, Type II