Higher expression of whole blood microRNA-21 in patients with ankylosing spondylitis associated with programmed cell death 4 mRNA expression and collagen cross-linked C-telopeptide concentration

J Rheumatol. 2014 Jun;41(6):1104-11. doi: 10.3899/jrheum.130515. Epub 2014 May 1.

Abstract

Objective: Bone loss is a recognized feature of ankylosing spondylitis (AS). The binding of microRNA-21 (miR-21) to programmed cell death 4 (PDCD4) could inhibit the expression of PDCD4 and further induce the activation of osteoclasts. In the present study, we compared the difference in miR-21 expression between patients with AS and healthy controls, and evaluated the relationships of miR-21, PDCD4 mRNA, and bone erosion in patients with AS. The influences of nonsteroidal antiinflammatory drugs (NSAID) and disease-modifying antirheumatic drugs (DMARD) on the expressions of miR-21 and PDCD4 mRNA in patients with AS were also assessed.

Methods: Whole blood miR-21 and PDCD4 mRNA expression were evaluated by quantitative real-time PCR among 122 patients with AS and 122 healthy controls. The serum level of collagen cross-linked C-telopeptide (CTX) was measured using ELISA.

Results: When compared to controls, patients with AS had significantly higher levels of miR-21, PDCD4 mRNA, and CTX. MiR-21 expression was negatively correlated with PDCD4 mRNA expression in patients with AS who were taking neither NSAID nor DMARD. Interestingly, significantly positive correlations between miR-21 expression with PDCD4 mRNA expression (r = 0.33, p = 0.01) and CTX level (r = 0.44, p < 0.01) were observed in patients with AS who were taking sulfasalazine. Positive correlations of miR-21 and CTX level were also observed in AS patients with disease duration < 7.0 years (r = 0.36, p = 0.004) and active disease (r = 0.42, p = 0.001).

Conclusion: The expression of miR-21 might have a role in the development of AS.

Keywords: ANKYLOSING SPONDYLITIS; COLLAGEN CROSS-LINKED C-TELOPEPTIDE; MICRORNA-21; PROGRAMMED CELL DEATH 4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antirheumatic Agents / therapeutic use
  • Apoptosis Regulatory Proteins / blood*
  • Apoptosis Regulatory Proteins / genetics
  • Collagen Type I / blood*
  • Collagen Type I / genetics
  • Female
  • Humans
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Peptides / blood*
  • Peptides / genetics
  • RNA, Messenger
  • RNA-Binding Proteins / blood*
  • RNA-Binding Proteins / genetics
  • Spondylitis, Ankylosing / blood*
  • Spondylitis, Ankylosing / drug therapy
  • Young Adult

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antirheumatic Agents
  • Apoptosis Regulatory Proteins
  • Collagen Type I
  • MIRN21 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • Peptides
  • RNA, Messenger
  • RNA-Binding Proteins
  • collagen type I trimeric cross-linked peptide