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Background: One of the etiologic components of degenerative spinal illnesses is intervertebral disc degeneration (IVDD), and the accompanying lower back pain is progressively turning into a significant public health problem. Important pathologic characteristics of IVDD include inflammation and acidic microenvironment, albeit it is unclear how these factors contribute to the disease. Purpose: To clarify the functions of inflammation and the acidic environment in IVDD, identify the critical connections facilitating glycolytic crosstalk and nucleus pulposus cells (NPCs) pyroptosis, and offer novel approaches to IVDD prevention and therapy. Methods: By developing keywords search strategy, literature was found and screened using databases such as PUBMED, Google Scholar, Web of Science, China National Knowledge Infrastructure, and others. Hub genes, protein interaction networks, clinical transcriptome data validation, and enrichment analysis were used to further validate relevant biological pathways. Results: It is clear that disc degeneration is associated with apoptosis or pyroptosis, inflammation, and an acidic environment based on literature review. The process of IVDD is intimately associated with pyroptosis, inflammation, and an acidic environment. The precise mechanism may entail the regulation of key genes such NLRP3, ASIC1a, IL1β, TNF-a, and GSDMD. While the acidic environment exacerbated extracellular matrix degradation and promoted cellular senescence and inflammatory factor expression, it was found to be unfavorable for NPCs survival and proliferation. Moreover, NPCs pyroptosis in an acidic environment, the molecular mechanism behind this phenomenon may be connected to ASIC1a mediated Ca + influx. On the other hand, IVDD can be constantly promoted by the interaction between the degenerating disc's acidic and inflammatory environments through "crosstalk" between anaerobic glycolysis and positive feedback. Conclusion: In summary, the inflammatory process in NPCs is made worse by the buildup of glucose brought on by metabolic problems, such as anaerobic glycolytic processes, and pyroptosis caused by excessive glucose may be mitigated by inhibiting endoplasmic reticulum stress. A new therapeutic approach for IVDD will involve using ASIC1a as a regulatory target to enhance the inflammatory environment and decrease the incidence of NPCs pyroptosis. Following this, anaerobic glycolysis will be regulated, lactic acid generation will be reduced, and the degenerative vicious loop will be blocked. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) is a bone metabolic disease caused by decreased bone mass leading to destruction of bone microstructure. Treatment of OP is characterized by a lifelong nature, causing extreme financial and psychological burdens to patients. Hormonal abnormalities, cellular autophagy, Ferroptosis, and oxidative stress are all part of the intricate and varied pathophysiology of OP. Recent research has revealed that mitochondrial dysfunction is a significant factor in the onset and progression of OP. By regulating bone marrow mesenchymal stem cell differentiation through various signaling pathways and cytokines, abnormal mitochondrial energy metabolism brought on by oxidative stress processes impacts osteoblast and osteoclast proliferation and differentiation, causing an imbalance in bone metabolism that ultimately results in OP. Therefore, one possible method to prevent and manage OP may be to use mitochondria as a carrier to trigger osteogenic differentiation of bone marrow mesenchymal stem cells from mitochondrial energy consumption, oxidative stress, autophagy, and osteoclast death. In order to offer some theoretical references and therapeutic approaches for the clinical prevention and treatment of OP, we will examine the pathophysiology of OP from mitochondrial dysfunction in this work., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2025. Published by Elsevier B.V.)

Background: Intervertebral disc degeneration disease (IVDD) is a prevalent orthopedic condition that causes chronic lower back pain, imposing a substantial economic burden on patients and society. Despite its high incidence, the pathophysiological mechanisms of IVDD remain incompletely understood., Objective: This study aimed to identify metabolomic alterations in IVDD patients and explore the key metabolic pathways and metabolites involved in its pathogenesis., Methods: Serum samples from 20 IVDD patients and 20 healthy controls were analyzed using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). The identified metabolites were mapped to metabolic pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database., Results: Significant alterations were observed in metabolites such as 2-methyl-1,3-cyclohexadiene, stearoyl sphingomyelin, methylcysteine, L-methionine, and cis, cis-muconic acid. These metabolites were involved in pathways including glycine, serine, and threonine metabolism, cyanoamino acid metabolism, and the citrate cycle (TCA cycle)., Conclusion: The identified metabolic alterations provide insights into the pathogenesis of IVDD and suggest potential therapeutic targets for future investigation., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)