Expression of osteoprotegerin and its ligands, RANKL and TRAIL, in rheumatoid arthritis

Sci Rep. 2016 Jul 12:6:29713. doi: 10.1038/srep29713.


Osteoprotegerin (OPG), receptor activator of nuclear factor-ΚB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been involved in rheumatoid arthritis (RA) pathophysiology. In this study, we assessed messenger RNA (mRNA) expression of these molecules by qPCR in peripheral blood from 26 patients with RA (12 of them with ischemic heart disease -IHD) and 10 healthy controls. Correlation coefficients between OPG, RANKL and TRAIL expression levels in RA patients and their clinical and demographic characteristics were also evaluated. Whereas OPG and OPG/TRAIL ratio expression were significantly increased in RA patients compared to controls (fold change = 1.79, p = 0.013 and 2.07, p = 0.030, respectively), RANKL/OPG ratio was significantly decreased (fold change = 0.50, p = 0.020). No significant differences were found between patients and controls in RANKL and TRAIL expression. Interestingly, TRAIL expression was significantly higher in RA patients with IHD compared to those without IHD (fold change = 1.46, p = 0.033). Moreover, biologic disease-modifying antirheumatic drugs (DMARDs) significantly decreased RANKL expression in RA patients (p = 0.016). Our study supports an important role of OPG and TRAIL in RA. Furthermore, it highlights an effect of biologic DMARDs in the modulation of RANKL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / administration & dosage
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / pathology
  • Female
  • Gene Expression Regulation*
  • Humans
  • Male
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / drug therapy
  • Myocardial Ischemia / pathology
  • Osteoprotegerin / blood*
  • RANK Ligand / blood*
  • TNF-Related Apoptosis-Inducing Ligand / blood*


  • Antirheumatic Agents
  • Osteoprotegerin
  • RANK Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF11B protein, human
  • TNFSF10 protein, human
  • TNFSF11 protein, human