2024/05/29 by Chun Tseng, Shan‐Chi Liu, Xiu-Yuan He +4 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Spine and Intervertebral Disc Pathology #Connective Tissue Growth Factor Research #Musculoskeletal pain and rehabilitation
paper · pdf · doi:10.18632/aging.205876
openalex publication_date 2024/05/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
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.