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<p>Intervertebral disc degeneration (IDD) is a common condition associated with aging and degeneration of the disc. Type 2 diabetes mellitus (T2DM) is linked to various musculoskeletal disorders, including IDD, but its molecular effects on IDD remain understudied. To explore the molecular differences in IDD between T2DM and non-T2DM patients, we conducted a quantitative proteomic analysis of nucleus pulposus (NP) tissues from patients with T2DM-IDD or non-T2DM-IDD individuals. We identified 3,720 proteins, with 221 significantly upregulated and 233 downregulated in T2DM-IDD. Multiple mitochondrial proteins were upregulated (NDUFV2, NDUFB5, NDUFA13, MPC2) indicating a potential increase in oxidative stress in the NP tissues from T2DM-IDD. Conversely, downregulated proteins such as versican (VCAN), an extracellular matrix proteoglycan, IL17B, a pro-inflammatory cytokine, and vascular endothelial growth factor A (VEGFA) indicate possible alterations in ECM composition and structure that impact the mechanical properties and integrity of the IVD as well as a reduced inflammatory response in NP tissues from non-T2DM-IDD. Additionally, T2DM-IDD showed enrichment in fatty acid metabolism pathways, while non-T2DM-IDD samples were enriched in epithelial mesenchymal transition and hypoxia pathways. Altogether, these results provide novel insights into the molecular mechanisms of T2DM-IDD and may guide future therapies.</p>

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Proteomic analysis identifies distinct signaling pathways in lumbar intervertebral disc degeneration between type-2 diabetic and non-diabetic patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月26日

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  • F M Moinuddin,
  • Jun Zhong,
  • Maria D. Astudillo Potes,
  • Asimina Dominari,
  • Ashis Dhar,
  • Akhilesh Pandey,
  • Mohamad Bydon

摘要

Intervertebral disc degeneration (IDD) is a common condition associated with aging and degeneration of the disc. Type 2 diabetes mellitus (T2DM) is linked to various musculoskeletal disorders, including IDD, but its molecular effects on IDD remain understudied. To explore the molecular differences in IDD between T2DM and non-T2DM patients, we conducted a quantitative proteomic analysis of nucleus pulposus (NP) tissues from patients with T2DM-IDD or non-T2DM-IDD individuals. We identified 3,720 proteins, with 221 significantly upregulated and 233 downregulated in T2DM-IDD. Multiple mitochondrial proteins were upregulated (NDUFV2, NDUFB5, NDUFA13, MPC2) indicating a potential increase in oxidative stress in the NP tissues from T2DM-IDD. Conversely, downregulated proteins such as versican (VCAN), an extracellular matrix proteoglycan, IL17B, a pro-inflammatory cytokine, and vascular endothelial growth factor A (VEGFA) indicate possible alterations in ECM composition and structure that impact the mechanical properties and integrity of the IVD as well as a reduced inflammatory response in NP tissues from non-T2DM-IDD. Additionally, T2DM-IDD showed enrichment in fatty acid metabolism pathways, while non-T2DM-IDD samples were enriched in epithelial mesenchymal transition and hypoxia pathways. Altogether, these results provide novel insights into the molecular mechanisms of T2DM-IDD and may guide future therapies.