Altered Metabolism and Inflammation Driven by Post-translational Modifications in Intervertebral Disc Degeneration.
Dingchao ZhuHuaizhen LiangZhi DuQian LiuGaocai LiWeifeng ZhangDi WuXingyu ZhouYu SongCao YangPublished in: Research (Washington, D.C.) (2024)
Intervertebral disc degeneration (IVDD) is a prevalent cause of low back pain and a leading contributor to disability. IVDD progression involves pathological shifts marked by low-grade inflammation, extracellular matrix remodeling, and metabolic disruptions characterized by heightened glycolytic pathways, mitochondrial dysfunction, and cellular senescence. Extensive posttranslational modifications of proteins within nucleus pulposus cells and chondrocytes play crucial roles in reshaping the intervertebral disc phenotype and orchestrating metabolism and inflammation in diverse contexts. This review focuses on the pivotal roles of phosphorylation, ubiquitination, acetylation, glycosylation, methylation, and lactylation in IVDD pathogenesis. It integrates the latest insights into various posttranslational modification-mediated metabolic and inflammatory signaling networks, laying the groundwork for targeted proteomics and metabolomics for IVDD treatment. The discussion also highlights unexplored territories, emphasizing the need for future research, particularly in understanding the role of lactylation in intervertebral disc health, an area currently shrouded in mystery.
Keyphrases
- extracellular matrix
- oxidative stress
- low grade
- induced apoptosis
- mass spectrometry
- high grade
- healthcare
- public health
- dna damage
- mental health
- multiple sclerosis
- dna methylation
- endothelial cells
- gene expression
- cell cycle arrest
- risk assessment
- heat stress
- drug delivery
- signaling pathway
- stress induced
- protein kinase
- human health
- health promotion