IL-17A enhances ADAMTS-7 expression through regulation of TNF-α in human nucleus pulposus cells

J Mol Histol. 2015 Dec;46(6):475-83. doi: 10.1007/s10735-015-9640-5. Epub 2015 Oct 7.

Abstract

ADMATS-7 is known to play an important role in the pathogenesis of various diseases, including cartilaginous diseases. IL-17A is an inflammatory cytokine detected in degenerative disc tissues. However, the interplay between IL-17A and ADMATS-7 in human disc degeneration is still unknown. Samples collected from 50 patients were divided into three groups according to MRI degeneration grading system score. Immunohistochemistry, RT-PCR and western Blotting were used to investigate the expression of ADAMTS-7 in NP tissues. Furthermore, a rat disc degeneration model was established, and the expression level of ADAMTS-7 was assayed using immunohistochemistry, RT-PCR and western Blotting. The human NP cells were cultured in the presence and absence of IL-17A stimulation. RNA extracts were collected, and real-time PCR was performed to determine the expression of ADAMTS-7. Moreover, ADAMTS-7 concentrations were detected in human NP cell culture supernatants by ELISA. After culturing NP cells with IL-17A (with or without Etanercept), ADAMTS-7 levels were detected in each group. ADAMTS-7 expression was dramatically elevated in both human and rat degenerative NP tissues compared with normal controls. The RT-PCR and ELISA results revealed that IL-17A could enhance the production of ADAMTS-7, while ADAMTS-7 expression dramatically decreased in the IL-17A + Etanercept group in comparison to the IL-17A alone group. Our results indicate the presence of ADAMTS-7 in human NP cells and imply its potential role in disc degeneration. Additionally, our results indicate that IL-17A induced ADAMTS-7 expression via TNF-α, which may form a molecular axis in human NP cells.

Keywords: ADAMTS-7; IL-17; Intervertebral disc (IVD) degeneration; TNF-α; The nucleus pulposus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics*
  • ADAM Proteins / metabolism
  • ADAMTS7 Protein
  • Adult
  • Aged
  • Animals
  • Disease Models, Animal
  • Etanercept / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Interleukin-17 / metabolism*
  • Interleukin-17 / pharmacology
  • Intervertebral Disc / cytology*
  • Intervertebral Disc / metabolism*
  • Intervertebral Disc Degeneration / genetics
  • Intervertebral Disc Degeneration / metabolism
  • Intervertebral Disc Degeneration / pathology
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Tumor Necrosis Factor-alpha / metabolism*
  • Young Adult

Substances

  • Interleukin-17
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • ADAM Proteins
  • ADAMTS7 Protein
  • ADAMTS7 protein, human
  • Etanercept