MicroRNA-125b regulates the expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes

Arthritis Res Ther. 2013 Feb 13;15(1):R28. doi: 10.1186/ar4164.


Introduction: Increased expression of aggrecanase-1 (ADAMTS-4) has emerged as an important factor in osteoarthritis (OA) and other joint diseases. This study aimed to determine whether the expression of ADAMTS-4 in human chondrocytes is regulated by miRNA.

Methods: MiRNA targets were identified using bioinformatics. Chondrocytes were isolated from knee cartilage and treated with interleukin-1 beta (IL-1β). Gene expression was quantified using TaqMan assays and protein production was determined by immunoblotting. Luciferase reporter assay was used to verify interaction between miRNA and target messenger RNA (mRNA).

Results: In silico analysis predicted putative target sequence of miR-125b on ADAMTS-4. MiR-125b was expressed in both normal and OA chondrocytes, with significantly lower expression in OA chondrocytes than in normal chondrocytes. Furthermore, IL-1β-induced upregulation of ADAMTS-4 was suppressed by overexpression of miR-125b in human OA chondrocytes. In the luciferase reporter assay, mutation of the putative miR-125b binding site in the ADAMTS-4 3'UTR abrogated the suppressive effect of miR125.

Conclusions: Our results indicate that miR-125b plays an important role in regulating the expression of ADAMTS-4 in human chondrocytes and this identifies miR-125b as a novel therapeutic target in OA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / biosynthesis*
  • ADAMTS4 Protein
  • Aged
  • Aged, 80 and over
  • Cartilage, Articular
  • Chondrocytes / enzymology*
  • Female
  • Gene Expression Regulation / genetics*
  • Humans
  • Immunoblotting
  • Male
  • MicroRNAs / genetics*
  • Osteoarthritis, Knee / enzymology
  • Osteoarthritis, Knee / genetics*
  • Procollagen N-Endopeptidase / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection


  • MIRN125 microRNA, human
  • MicroRNAs
  • ADAM Proteins
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein
  • ADAMTS4 protein, human