HIF-1α protects osteoblasts from ROS-induced apoptosis

Abstract

The regulatory mechanism of hypoxia-inducible factor-1α (HIF-1α) is complex. HIF-1α may inhibit or promote apoptosis in osteoblasts under different physiological conditions, and induce bone regeneration and repair injury in coordination with angiogenesis. The relationship between H₂O₂ and HIFs is complex, and this study aimed to explore the role of HIF-1α in H₂O₂-induced apoptosis. Dimethyloxallyl glycine (DMOG) and 2-Methoxyestradiol (2ME) were used to stabilize and inhibit HIFs, respectively. Cell viability was assessed with CCK8. Apoptosis and ROS levels were detected by flow cytometry, and HIF mRNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR). Western blot was performed to detect HIF-1α, HIF-2α, Bax, Bak, Bcl-2, Bcl-XL, caspase-9, and PCNA protein amounts. Our data suggest that both HIF-1α and HIF-2α play a protective role in oxidative stress. HIF-1α reduces H₂O₂-induced apoptosis by upregulating Bcl-2 and Bcl-XL, downregulating Bax, Bak, and caspase-9, stabilizing intracellular ROS levels, and promoting the repair of H₂O₂-induced DNA damage to reduce apoptosis.

Keywords:

• HIF-1α
• HIF-2α
• ROS

Acknowledgments

The authors thanks for the financial support from the National Natural Science Foundation of China (number: 81960038). The authors thanked Dongxiao Wang for technical assistances with the Western blot.

Disclosure statement

All the authors have no financial conflict of interest to disclose. The authors are responsible for the content and writing of the article.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [number: 81960038]. National Natural Science Foundation of China (Number 82060029)