title: MiR-34a promotes Fas-mediated cartilage endplate chondrocyte apoptosis by targeting Bcl-2.
abstract: Apoptosis of cartilage endplate (CEP) chondrocytes is associated with the pathogenesis of intervertebral disk degeneration (IDD). Recent studies have shown that miR-34a is crucially involved in chondrocyte apoptosis during osteoarthritic cartilage. Here, we investigated the involvement of miR-34a in CEP chondrocyte apoptosis in IDD. In human degenerated CEP chondrocytes, miRNA (miR)-34a was markedly elevated in association with increased apoptosis. Bioinformatics target prediction identified Bcl-2 as a putative target of miR-34a. Furthermore, miR-34a inhibited Bcl-2 expression by directly targeting their 3'-untranslated regions, and this inhibition was abolished by mutation of the miR-34a binding sites. In vitro, knockdown of miR-34a in human endplate chondrocytes resulted in overexpression of Bcl-2, whereas upregulation of miR-34a led to repression of Bcl-2. Fas-mediated apoptosis was decreased when antagonizing miR-34a with locked nucleotide analog-miR-34a in human endplate chondrocytes. Taken together, our results demonstrate that upregulated miR-34a potentiates Fas-mediated endplate chondrocyte apoptosis, which is associated with IDD.
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Feng Yang Road, Shanghai, 200003, People's Republic of China, doctorchj@126.com.
authors.forename: Huajiang
authors.initials: H
authors.lastname: Chen
authors.forename: Jianxi
authors.initials: J
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wu
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Renhu
authors.initials: R
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000368:Aged; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D002356:Cartilage / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D005260:Female; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C000595707:BCL2 protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor