Journal of Bone and Mineral Metabolism

, Volume 33, Issue 1, pp 40–47

A significant induction of neutrophilic chemoattractants but not RANKL in synoviocytes stimulated with interleukin 17

  • Muneo Ota
  • Maiko Yanagisawa
  • Hideyuki Tachibana
  • Kazuhiro Yokota
  • Yasuto Araki
  • Kojiro Sato
  • Toshihide Mimura
Original Article


Interleukin 17 (IL-17) is a cytokine implicated in the promotion of osteoclastogenesis. Its effect has been believed not to be directly exerted on osteoclast precursors, but rather indirectly carried out via an induction of receptor activator of NF-κB ligand (RANKL), the osteoclast differentiation factor, on osteoclast-supporting cells, which in turn exert an effect on osteoclast precursors. The mechanistic details, however, remain unclear. In this study, we first performed a transcriptome analysis of synoviocytes derived from a patient with rheumatoid arthritis cultured in the presence or absence of IL-17. We discovered that most of the genes significantly induced by IL-17 were chemokines with a chemotactic effect on neutrophils. We confirmed these results by quantitative RT-PCR and ELISA. Unexpectedly, the stimulation with IL-17 alone did not induce the expression of RANKL either at the mRNA or the protein level. The induction of RANKL was observed when IL-17 was added in combination with 1,25-dihydroxyvitamin D3 and prostaglandin E2, well-known inducers of RANKL, although the exact mechanism of this synergistic effect remains unclear. IL-6 and monocyte chemoattractant protein-1 were also significantly induced by IL-17 at both the mRNA and protein levels. Thus, it appears that IL-17 induces the migration of neutrophils and monocytes/macrophages through the activation of synoviocytes, and enhances a positive feedback loop composed of proinflammatory cytokines IL-6 and IL-17.


Interleukin 17 Osteoclast Synoviocytes Rheumatoid arthritis 





Receptor activator of NF-κB ligand


Rheumatoid arthritis


Osteoclast differentiation factor


Macrophage colony stimulating factor




Fetal calf serum


Chemokine (C–X–C motif) ligand


Chemokine (C–C motif) ligand


1,25-dihydroxyvitamin D3


Prostaglandin E2


Tartrate-resistant acid phosphatase


Monocyte chemoattractant protein-1

Supplementary material

774_2014_565_MOESM1_ESM.pdf (27 kb)
Supplementary material 1 (PDF 27 kb)


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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan 2014

Authors and Affiliations

  • Muneo Ota
    • 1
  • Maiko Yanagisawa
    • 1
  • Hideyuki Tachibana
    • 1
  • Kazuhiro Yokota
    • 1
  • Yasuto Araki
    • 1
  • Kojiro Sato
    • 1
  • Toshihide Mimura
    • 1
  1. 1.Department of Rheumatology and Applied Immunology, Faculty of MedicineSaitama Medical UniversityIruma-gunJapan

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