title: Effect of microRNA-21 on the proliferation of human degenerated nucleus pulposus by targeting programmed cell death 4.
abstract: This study aims to explore the effect of microRNA-21 (miR-21) on the proliferation of human degenerated nucleus pulposus (NP) by targeting programmed cell death 4 (PDCD4) tumor suppressor. NP tissues were collected from 20 intervertebral disc degeneration (IDD) patients, and from 5 patients with traumatic spine fracture. MiR-21 expressions were tested. NP cells from IDD patients were collected and divided into blank control group, negative control group (transfected with miR-21 negative sequences), miR-21 inhibitor group (transfected with miR-21 inhibitors), miR-21 mimics group (transfected with miR-21 mimics) and PDCD4 siRNA group (transfected with PDCD4 siRNAs). Cell growth was estimated by Cell Counting Kit-8; PDCD4, MMP-2,MMP-9 mRNA expressions were evaluated by qRT-PCR; PDCD4, c-Jun and p-c-Jun expressions were tested using western blot. In IDD patients, the expressions of miR-21 and PDCD4 mRNA were respectively elevated and decreased (both P<0.05). The miR-21 expressions were positively correlated with Pfirrmann grades, but negatively correlated with PDCD4 mRNA (both P<0.001). In miR-21 inhibitor group, cell growth, MMP-2 and MMP-9 mRNA expressions, and p-c-Jun protein expressions were significantly lower, while PDCD4 mRNA and protein expressions were higher than the other groups (all P<0.05). These expressions in the PDCD4 siRNA and miR-21 mimics groups was inverted compared to that in the miR-21 inhibitor group (all P<0.05). MiR-21 could promote the proliferation of human degenerated NP cells by targeting PDCD4, increasing phosphorylation of c-Jun protein, and activating AP-1-dependent transcription of MMPs, indicating that miR-21 may be a crucial biomarker in the pathogenesis of IDD.
authors.affiliation: Department of Orthopedics, Linyi Second People's Hospital, Linyi, China.
authors.forename: B
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Linyi Second People's Hospital, Linyi, China.
authors.forename: S G
authors.initials: SG
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, Linyi Second People's Hospital, Linyi, China.
authors.forename: L
authors.initials: L
authors.lastname: Ju
authors.affiliation: Department of Orthopedics, Linyi Second People's Hospital, Linyi, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Linyi Second People's Hospital, Linyi, China.
authors.forename: F F
authors.initials: FF
authors.lastname: Nie
authors.affiliation: Department of General Surgery, Affiliated Hospital of Taishan Medical University, Taian, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Linyi Second People's Hospital, Linyi, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Linyi Second People's Hospital, Linyi, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Linyi Second People's Hospital, Linyi, China.
authors.forename: F
authors.initials: F
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002452:Cell Count; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000378:metabolism; D008156:Luciferases; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000070614:Nucleus Pulposus / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016103:Spinal Fractures / Q000378:metabolism; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D008156:Luciferases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9