Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
✉ Corresponding authors: Qiang Zhou, Ph.D., Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Email: zhouqiangcqmu.edu.cn. Tel: 86-13377669899. Pei Li, Ph.D., Department of Orthopedics, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Email: lipeicqmu.edu.cn. Tel: 86-15102346483.More
Citation:
Zou L, Wang Y, Hu Y, Liu L, Luo L, Chen Z, Zhuo Y, Li P, Zhou Q. N-cadherin Alleviates Apoptosis and Senescence of Nucleus Pulposus Cells via Suppressing ROS-dependent ERS in the Hyper-osmolarity Microenvironment. Int J Med Sci 2024; 21(2):341-356. doi:10.7150/ijms.90591. https://www.medsci.org/v21p0341.htm
The in-situ osmolarity is an important physicochemical factor that regulates cell fate of nucleus pulposus cells (NPCs). Our previous studies demonstrated that reduced N-cadherin (NCDH) expression in nucleus pulposus cells is associated with cellular damage under hyper-osmolarity microenvironment. This study was aimed at exploring the impacts of NCDH on senescence and apoptosis of NPCs, as well as the potential molecular mechanism. By comparing NPCs from patients with lumbar fractures and lumbar disc herniation, we identified a correlation between decreased NCDH expression and increased endoplasmic reticulum stress (ERS), resulting in undesirable cell fate (senescence and apoptosis). After blocking Reactive oxygen species (ROS) or ERS, it was indicated that hyper-osmolarity microenvironment induced ERS was ROS-dependent. Further results demonstrated the correlation in rat NPCs. Upregulation of NCDH expression reduced ROS-dependent ERS, thus limiting undesirable cell fates in vitro. This was further confirmed through the rat tail acupuncture injection model. NCDH overexpression successfully mitigated ERS, preserved extracellular matrix production and alleviating intervertebral disc degeneration in vivo. Together, NCDH can alleviate senescence and apoptosis of NPCs by suppressing ROS-dependent ERS via the ATF4-CHOP signaling axis in the hyper-osmolarity microenvironment, thus highlighting the therapeutic potential of NCDH in combating degenerative disc diseases.
Zou, L., Wang, Y., Hu, Y., Liu, L., Luo, L., Chen, Z., Zhuo, Y., Li, P., Zhou, Q. (2024). N-cadherin Alleviates Apoptosis and Senescence of Nucleus Pulposus Cells via Suppressing ROS-dependent ERS in the Hyper-osmolarity Microenvironment. International Journal of Medical Sciences, 21(2), 341-356. https://doi.org/10.7150/ijms.90591.
ACS
Zou, L.; Wang, Y.; Hu, Y.; Liu, L.; Luo, L.; Chen, Z.; Zhuo, Y.; Li, P.; Zhou, Q. N-cadherin Alleviates Apoptosis and Senescence of Nucleus Pulposus Cells via Suppressing ROS-dependent ERS in the Hyper-osmolarity Microenvironment. Int. J. Med. Sci. 2024, 21 (2), 341-356. DOI: 10.7150/ijms.90591.
NLM
Zou L, Wang Y, Hu Y, Liu L, Luo L, Chen Z, Zhuo Y, Li P, Zhou Q. N-cadherin Alleviates Apoptosis and Senescence of Nucleus Pulposus Cells via Suppressing ROS-dependent ERS in the Hyper-osmolarity Microenvironment. Int J Med Sci 2024; 21(2):341-356. doi:10.7150/ijms.90591. https://www.medsci.org/v21p0341.htm
CSE
Zou L, Wang Y, Hu Y, Liu L, Luo L, Chen Z, Zhuo Y, Li P, Zhou Q. 2024. N-cadherin Alleviates Apoptosis and Senescence of Nucleus Pulposus Cells via Suppressing ROS-dependent ERS in the Hyper-osmolarity Microenvironment. Int J Med Sci. 21(2):341-356.
This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.