MiR-98 promotes chondrocyte apoptosis by decreasing Bcl-2 expression in a rat model of osteoarthritis

Acta Biochim Biophys Sin (Shanghai). 2016 Oct;48(10):923-929. doi: 10.1093/abbs/gmw084. Epub 2016 Sep 2.

Abstract

Altered expression of miRNA-98 (miR-98) has been reported in osteoarthritis (OA) patients, while its role and underlying mechanisms remain elusive. In the present study, a rat model of OA was established using modified Hulth method, and the expression level of miR-98 and its effect on cartilage degradation and cell apoptosis in OA rats were examined. The results showed that up-regulated miR-98 was observed in OA rats, and knockdown of miR-98 in OA rats resulted in an inhibitory effect on cartilage degradation and chondrocyte apoptosis. Then the potential apoptosis associated genes regulated by miR-98 were screened and examined in cartilage tissues. The target gene of miR-98 was validated by luciferase reporter assay. The data showed that the increased miR-98 was accompanied with a reduced expression of Bcl-2 at both mRNA and protein levels. Furthermore, the silencing of miR-98 in OA rats prevented the down-regulation of Bcl-2 in cartilage tissues. Finally, the luciferase reporter assay validated that Bcl-2 was the target gene of miR-98. In this study, we found that miR-98 might promote chondrocyte apoptosis and cartilage degradation by down-regulating Bcl-2 expression in the pathogenesis of OA, suggesting that miR-98 can be a potential target for the treatment of OA.

Keywords: Bcl-2; apoptosis; microRNA-98; osteoarthritis.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Apoptosis / genetics*
  • Base Sequence
  • Blotting, Western
  • Cartilage, Articular / metabolism
  • Chondrocytes / metabolism*
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • MicroRNAs / genetics*
  • Osteoarthritis / genetics*
  • Osteoarthritis / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid

Substances

  • 3' Untranslated Regions
  • MIRN98 microRNA-98, rat
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2