Research Paper Volume 15, Issue 6 pp 2275—2292
PTEN inhibitor VO-OHpic protects endplate chondrocytes against apoptosis and calcification via activating Nrf-2 signaling pathway
- 1 Department of Spine Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250000, China
- 2 Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250000, China
- 3 Department of Orthopaedics, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, China
- 4 Department of Medical, Yidu Cloud (Beijing) Technology Co. Ltd., Beijing 100191, China
Received: December 2, 2022 Accepted: March 15, 2023 Published: March 24, 2023
https://doi.org/10.18632/aging.204612How to Cite
Copyright: © 2023 Cui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Cartilage endplate (CEP) degeneration and calcification is an important contributor to the onset and pathogenesis of intervertebral disc degeneration (IDD). However, the underlying mechanisms of CEP degeneration remain elusive, let alone according treatment strategies to prevent CEP degeneration. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene that promotes cell apoptosis, and recent studies indicated that PTEN is overexpressed in degenerated intervertebral disc. However, whether direct inhibition of PTEN attenuates CEP degeneration and IDD development remains largely unknown. In the present study, our in vivo experiments demonstrated that VO-OHpic could attenuate IDD progression and CEP calcification. We also found that VO-OHpic inhibited oxidative stress induced chondrocytes apoptosis and degeneration by activating Nrf-2/HO-1 pathway, thus promoted parkin mediated mitophagy process and inhibited chondrocytes ferroptosis, alleviated redox imbalance and eventually improved cell survival. Nrf-2 siRNA transfection significantly reversed the protective effect of VO-OHpic on endplate chondrocytes. In conclusion, our study demonstrated that inhibition of PTEN with VO-OHpic attenuates CEP calcification and IDD progression. Moreover, VO-OHpic protects endplate chondrocytes against apoptosis and degeneration via activating Nrf-2/HO-1 mediated mitophagy process and ferroptosis inhibition. Our results suggest that VO-OHpic may be a potential effective medicine for IDD prevention and treatment.