miR-214 stimulated by IL-17A regulates bone loss in patients with ankylosing spondylitis

Rheumatology (Oxford). 2020 May 1;59(5):1159-1169. doi: 10.1093/rheumatology/kez594.

Abstract

Objective: Bone loss is common in AS, and miR-214 plays an important role in regulating bone formation. The aim of this study was to investigate the effect of miR-214, the production of which is stimulated by IL-17A, on bone loss in AS.

Methods: Peripheral blood was obtained from 32 patients with AS and 24 healthy controls. Levels of IL-17A, soluble RANK ligand (RANKL) and osteoprotegerin in serum were evaluated by ELISA, and the relative level of miR-214 in serum was detected by real-time quantitative PCR. In addition, we assessed the relationship between levels of miR-214, IL-17A and bone loss in primary murine osteoblasts and mouse bone marrow cells.

Results: The expression of RANKL and miR-214 in osteoblasts was increased following stimulation by IL-17A, and osteoblasts stimulated by IL-17A promoted the expression of miR-214 in osteoclasts and the activity of osteoclasts. We showed that osteoblast-derived miR-214 could be transferred to osteoclasts and could then regulate their activity. The levels of IL-17A and miR-214 were much higher in the serum of patients with AS than in that of healthy controls, and the relative level of miR-214 was positively correlated with the level of IL-17A in the serum and synovial fluid of the patients with AS, not healthy controls. The level of miR-214 in the serum of AS patients has potential diagnostic value.

Conclusion: The production of miR-214 in osteoblasts is stimulated by IL-17A. It is an important inhibitor of bone formation in AS, and the serum level of miR-214 might be of potential diagnostic value for AS.

Keywords: IL-17A; ankylosing spondylitis; bone loss; miR-214.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption
  • Case-Control Studies
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-17 / metabolism*
  • Male
  • Mice
  • MicroRNAs / metabolism
  • Osteoclasts / metabolism
  • Osteogenesis*
  • RANK Ligand / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Reference Values
  • Spondylitis, Ankylosing / blood*
  • Spondylitis, Ankylosing / metabolism*
  • Translational Research, Biomedical

Substances

  • IL17A protein, human
  • Interleukin-17
  • MIRN214 microRNA, human
  • MicroRNAs
  • RANK Ligand