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Research Paper|Volume 16, Issue 11|pp 9460—9469

High glucose enhances fibrosis in human annulus fibrosus cells by activating mTOR, PKCδ, and NF-κB signaling pathways

Chun Tseng1,2,3,4, Shan-Chi Liu5, Xiu-Yuan He6, Hsien-Te Chen2,3,7, Pang-Hsuan Hsiao2,3, Yi-Chin Fong2,4,7, Chih-Hsin Tang1,6,8,9,10
  • 1Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
  • 2Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
  • 3Spine Center, China Medical University Hospital, Taichung, Taiwan
  • 4Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan
  • 5Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan
  • 6Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
  • 7Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
  • 8Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
  • 9Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan
  • 10Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
Received: January 19, 2024Accepted: April 10, 2024Published: May 29, 2024
https://doi.org/10.18632/aging.205876

Copyright: © 2024 Tseng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Low back pain stands as a significant factor in disability, largely resulting from intervertebral disc degeneration (IVDD). High glucose (HG) levels have been implicated in the pathogenesis of IVDD. However, the detailed mechanism of HG in IVDD is largely unknown. Our clinical results revealed that fibrosis markers such as CTGF, Col1a1, ATF4, and EIF2 are highly expressed in advanced-stage IVDD patients. Stimulation of human annulus fibrosus cells (HAFCs) with HG, but not mannitol, promotes fibrosis protein production. Ingenuity Pathway Analysis in the GSE database found that the mTOR, PKCδ, and NF-κB pathways were significantly changed during IVDD. The mTOR, PKCδ, and NF-κB inhibitors or siRNAs all abolished HG-induced fibrosis protein production. In addition, treatment of HAFCs with HG enhances the activation of mTOR, PKCδ, and NF-κB pathways. Thus, HG facilitates fibrosis in IVDD through mTOR, PKCδ, and NF-κB pathways. These results underscore the critical role of HG as a fibrotic factor in the progression of IVDD.