Research Paper Volume 12, Issue 23 pp 24168—24183
Oxidative stress mediates age-related hypertrophy of ligamentum flavum by inducing inflammation, fibrosis, and apoptosis through activating Akt and MAPK pathways
- 1 Department of Orthopaedic Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- 2 Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- 3 Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- 4 Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- 5 Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan
- 6 Department of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan
- 7 Department of Orthopedics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- 8 Skeleton Materials and Bio-compatibility Core Lab, Research Center of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- 9 Medical Device Innovation Center (MDIC), National Cheng Kung University, Tainan, Taiwan
Received: June 25, 2020 Accepted: August 31, 2020 Published: November 20, 2020
https://doi.org/10.18632/aging.104105How to Cite
Copyright: © 2020 Chuang 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
The role of oxidative stress in ligamentum flavum (LF) hypertrophy has not been elucidated. We hypothesize that oxidative stress induces inflammatory responses and the subsequent fibrotic processes in LF, via activation of the Akt and MAPK pathways. Specimens of LFs were collected during surgeries for lumbar disc herniation (LDH) or lumbar spinal stenosis (LSS). Part of the LF specimens underwent analyses for ROS, fibrotic markers, and inflammatory mediators, with the remainder minced for cell cultures. The cell cultures were treated with H2O2, after which the cells were lysed and analyzed via western blotting. The specimens of the LSS patients showed increased infiltration of inflammatory cells and were stained positively for MMP-3, MMP-9, vimentin, and fibronectin. The LF of the LSS patients had increased oxidative stress and inflammation compared to that of the LDH patients. In vitro analyses demonstrated that oxidative stress rapidly activated the Akt and MAPK pathways. Inflammatory mediators, iNOS and NF-κB, and fibrotic markers, including TGF-β, β-catenin, α-SMA and vimentin, were significantly upregulated after induction of oxidative stress. Oxidative stress activated the intrinsic apoptotic pathway. These findings revealed that oxidative stress is one of the etiological factors of LF hypertrophy, which might provide new insights into treatment approaches.