IL-17A regulates the autophagic activity of osteoclast precursors through RANKL-JNK1 signaling during osteoclastogenesis in vitro

Biochem Biophys Res Commun. 2018 Mar 11;497(3):890-896. doi: 10.1016/j.bbrc.2018.02.164. Epub 2018 Feb 21.

Abstract

Interleukin-17A(IL-17A), a proinflammatory cytokine, may have effects on osteoclastic resorption in inflammation-mediated bone loss, including postmenopausal osteoporosis. IL-17A could alter autophagic activity among other tissues and cells, thereby causing corresponding lesions. The aim of this study was to clarify how IL-17A influenced osteoclastogenesis by regulating autophagy. The present study showed that IL-17A could facilitate osteoclast precursors (OCPs) autophagy and osteoclastogenesis at a low concentration. Furthermore, suppression of autophagy with chloroquine (CQ) or 3-MA could significantly attenuate the enhanced osteoclastogenesis by a low level of IL-17A. It was also found that a low level of IL-17A couldn't up-regulate OCPs autophagy after removal of RANKL(Receptor Activator for Nuclear Factor-κB Ligand), and JNK(c-Jun N-terminal kinase) inhibitor only inhibited autophagy at a low level of IL-17A. These results suggest that a low concentration of IL-17A is likely to promote autophagic activity via activating RANKL-JNK pathway during osteoclastogenesis.

Keywords: Autophagy; IL-17A; JNK; Osteoclast; RANKL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Cell Differentiation
  • Interleukin-17 / metabolism*
  • MAP Kinase Signaling System
  • Mice
  • Mitogen-Activated Protein Kinase 8 / metabolism*
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism
  • RANK Ligand / metabolism*
  • RAW 264.7 Cells
  • Signal Transduction*
  • TNF Receptor-Associated Factor 3 / metabolism

Substances

  • Il17a protein, mouse
  • Interleukin-17
  • RANK Ligand
  • TNF Receptor-Associated Factor 3
  • Tnfsf11 protein, mouse
  • Mitogen-Activated Protein Kinase 8