Affordable Access

deepdyve-link
Publisher Website

Hepatocyte growth factor regulates HIF-1α-induced nucleus pulposus cell proliferation through MAPK-, PI3K/Akt-, and STAT3-mediated signaling.

Authors
  • Itsuji, Tomonori1
  • Tonomura, Hitoshi1
  • Ishibashi, Hidenobu1
  • Mikami, Yasuo2
  • Nagae, Masateru1
  • Takatori, Ryota1
  • Tanida, Takashi3
  • Matsuda, Ken-Ichi3
  • Tanaka, Masaki3
  • Kubo, Toshikazu1
  • 1 Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. , (Japan)
  • 2 Department of Rehabilitation Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. , (Japan)
  • 3 Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. , (Japan)
Type
Published Article
Journal
Journal of Orthopaedic Research®
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jun 01, 2021
Volume
39
Issue
6
Pages
1184–1191
Identifiers
DOI: 10.1002/jor.24679
PMID: 32242977
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Intervertebral discs are important for maintaining mobility and offer support to the body trunk. If these discs lose their biomechanical features, lower back pain can occur. We previously reported that hepatocyte growth factor (HGF) promotes cell proliferation and suppresses apoptosis, inflammation, and matrix degradation in nucleus pulposus (NP) cells. In the present study, we investigated the molecular mechanisms of how HGF promotes the proliferation of NP cells in hypoxic conditions. Hypoxic stimulation promoted modest cell proliferation, which was further upregulated by HGF. Expression of hypoxia-inducible factor (HIF-1α) protein, which contributes to the maintenance of homeostasis in NP cells, was also upregulated in hypoxia-treated cell groups; HGF further increased HIF-1α expression in NP cells. Additionally, knockdown of HIF-1α expression significantly reduced the proliferation of NP cells. An MAPK inhibitor inhibited the expression of HIF-1α and pERK, as well as cell proliferation in a dose-dependent manner. Similarly, inhibiting the PI3K/Akt and STAT3 pathways also decreased the expression of HIF-1α and cell proliferation. These results show that under hypoxic conditions, HGF promotes NP cell proliferation via HIF-1α-, MAPK-, PI3K/Akt-, and STAT3-mediated signaling which is involved in this pathway. The control of these signaling pathways may be a target for potential therapeutic strategies for the treatment of disc degeneration in hypoxic conditions. © 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Report this publication

Statistics

Seen <100 times