Journal of Orthopaedic Surgery and Research (May 2023)

Hypoxia regulates adipose mesenchymal stem cells proliferation, migration, and nucleus pulposus-like differentiation by regulating endoplasmic reticulum stress via the HIF-1α pathway

  • Jianxin Wu,
  • Lei Yu,
  • Yi Liu,
  • Bing Xiao,
  • Xiaojian Ye,
  • Hong Zhao,
  • Yanhai Xi,
  • Zhicai Shi,
  • Weiheng Wang

DOI
https://doi.org/10.1186/s13018-023-03818-1
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 13

Abstract

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Abstract Objective Hypoxia can promote stem cell proliferation and migration through HIF-1α. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-α, and ER stress, however, while little is known about HIF-α and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1α and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation. Method ADSCs were pretreated with hypoxia, HIF-1α gene transfection, and HIF-1α gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1α in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1α in ADSCs under hypoxic conditions. Result The cell proliferation and migration assay results show that hypoxia and HIF-1α overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1α inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1α and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1α pathway, thereby regulating the cellular state of ADSCs, was also observed. Conclusion Hypoxia and HIF-1α play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1α-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1α and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration.

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