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

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

Automated summary

This study investigates the impact of hypoxia on adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation through the regulation of HIF-1a and ER stress. The results show that hypoxia and HIF-1a overexpression increase ADSCs proliferation and migration, while HIF-1a inhibition reduces these processes. Additionally, hypoxia regulates ER stress in ADSCs through the HIF-1a pathway.