Academic Journal
Role of the GAPDH-mediated glycolysis-senescence axis in osteoarthritis chondrocytes and its modulation by semaglutide.
| Τίτλος: | Role of the GAPDH-mediated glycolysis-senescence axis in osteoarthritis chondrocytes and its modulation by semaglutide. |
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| Συγγραφείς: | Liu D; Department of Orthopedics, The Second Affiliated Hospital of Bengbu Medical University, No. 633 Longhua Road, Huaishang District, Bengbu, 233000 Anhui, China; Anhui Key Laboratory of Computational Medicine and Intelligent Health, Bengbu Medical University, No. 2600 Donghai Avenue, Bengbu, 233000 Anhui, China. Electronic address: m18297312520@163.com., Wang L; Department of Urology, The First Affiliated Hospital of Bengbu Medical University, No. 287 Changhuai Road, Bengbu, 233004 Anhui, China., Zhu L; School of Basic Medical Sciences, Bengbu Medical University, No. 2600 Donghai Avenue, Bengbu, 233030 Anhui, China., Wang Y; School of Basic Medical Sciences, Bengbu Medical University, No. 2600 Donghai Avenue, Bengbu, 233030 Anhui, China., Pei L; Department of Orthopedics, the First Affiliated Hospital of Bengbu Medical University, 233004 Anhui, China. |
| Πηγή: | Joint bone spine [Joint Bone Spine] 2026 Oct; Vol. 93 (5), pp. 106072. Date of Electronic Publication: 2026 May 08. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Editions Elsevier Country of Publication: France NLM ID: 100938016 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1778-7254 (Electronic) Linking ISSN: 1297319X NLM ISO Abbreviation: Joint Bone Spine Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Paris : Editions Elsevier, c2000- |
| Ιατρικοί όροι (MeSH): | Chondrocytes*/metabolism , Chondrocytes*/drug effects , Osteoarthritis*/metabolism , Osteoarthritis*/genetics , Osteoarthritis*/pathology , Osteoarthritis*/drug therapy , Cellular Senescence*/drug effects , Cellular Senescence*/genetics , Glycolysis*/drug effects , Glycolysis*/genetics , Glucagon-Like Peptides*/pharmacology , Glyceraldehyde-3-Phosphate Dehydrogenases*/genetics, Cell Proliferation/drug effects ; Semaglutide ; Humans ; Cells, Cultured ; Oxidative Stress |
| Περίληψη: | Objectives: This study aimed to identify key regulatory genes involved in chondrocyte senescence in osteoarthritis (OA) and to evaluate the therapeutic potential of the GLP-1 receptor agonist semaglutide. Methods: Transcriptomic data of chondrocytes from OA and control groups were collected. Batch effects were corrected using Harmony, and differential expression analysis was performed with DESeq2 to identify significantly altered genes. Functional enrichment and pathway involvement were assessed using KEGG and Gene Set Enrichment Analysis (GSEA). Weighted gene co-expression network analysis (WGCNA) was applied to identify OA-related modules, and protein-protein interaction (PPI) networks were constructed to screen for hub genes. In vitro experiments included ROS detection, RT-PCR, and ELISA to evaluate oxidative stress, inflammatory mediators, and senescence-associated gene expression. Cell proliferation was assessed using CCK-8, and semaglutide treatment at different concentrations was applied to verify its regulatory effects. Results: Transcriptomic analysis revealed significant upregulation of inflammatory and oxidative stress pathways in OA chondrocytes, accompanied by downregulation of cell cycle and DNA repair pathways, suggesting the accumulation of senescent cells. WGCNA and PPI network analyses identified GAPDH as a key hub gene, whose expression was markedly reduced in OA. In vitro validation confirmed decreased proliferative capacity, elevated ROS levels, and increased expression of p53, IL-6, and TGF-β in OA cells. Semaglutide treatment reversed GAPDH downregulation, improved proliferation, and reduced p53 and inflammatory cytokine levels, suggesting that it exerts protective effects through modulation of the glycolysis-senescence-inflammation axis. Conclusion: This study systematically elucidates the senescence-centered pathological characteristics of OA chondrocytes and identifies GAPDH as a pivotal regulator of glycolysis and senescence. Semaglutide alleviates OA progression by restoring GAPDH expression and modulating metabolic-senescence signaling. These findings provide a theoretical basis for metabolism- and senescence-targeted interventions in OA and offer new insights into potential molecular therapeutic targets. (Copyright © 2026 Société Française de Rhumatologie. Published by Elsevier Masson SAS. All rights reserved.) |
| Contributed Indexing: | Keywords: Cellular senescence; Chondrocytes; GAPDH; Osteoarthritis; Semaglutide |
| Substance Nomenclature: | 53AXN4NNHX (Semaglutide) 62340-29-8 (Glucagon-Like Peptides) EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases) |
| Entry Date(s): | Date Created: 20260510 Date Completed: 20261007 Latest Revision: 20261007 |
| Update Code: | 20261008 |
| DOI: | 10.1016/j.jbspin.2026.106072 |
| PMID: | 42107588 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1778-7254 |
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| DOI: | 10.1016/j.jbspin.2026.106072 |