MiR-34a promotes Fas-mediated cartilage endplate chondrocyte apoptosis by targeting Bcl-2

• DOI: 10.1007/s11010-015-2420-4
• Publication Date: 2015-04-24T14:22:18Z
• Authors: Huajiang Chen; Jianxi Wang; Bo Hu; Xiaodong Wu; Yu Chen; Renhu Li; Wen Yuan
• Keywords: Male; 0301 basic medicine; 0303 health sciences; Binding Sites; Base Sequence; Apoptosis; Intervertebral Disc Degeneration; Middle Aged; MicroRNAs; 03 medical and health sciences; Cartilage; Chondrocytes; Proto-Oncogene Proteins c-bcl-2; Humans; Female; RNA Interference; fas Receptor; Cells, Cultured; Aged

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.