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<p>This study delved into the molecular mechanisms underlying mechanical stress-induced intervertebral disc degeneration (msi-IDD) through single-cell and high-throughput transcriptome sequencing in mouse models and patient samples. Results exhibited an upsurge in macrophage presence in msi-IDD intervertebral disc (IVD) tissues, with secreted phosphoprotein 1 (SPP1) identified as a pivotal driver exacerbating degeneration via the protein kinase RNA-like endoplasmic reticulum kinase/ activating transcription factor 4/ interleukin-10 (PERK/ATF4/IL-10) signaling axis. Inhibition of SPP1 demonstrated promising outcomes in mitigating msi-IDD progression in both in vitro and in vivo models. These findings underscore the therapeutic promise associated with the modulation of the PERK signaling pathway in IDD, shedding light on the pathogenesis of msi-IDD and proposing a promising avenue for intervention strategies.</p> Graphical abstract <p>1) Macrophage Regulation in IDD: SPP1 activates the PERK/ATF4/IL-10 signaling axis in macrophages, increasing IL-10 production, essential for inhibiting msi-IDD progression.</p> <p>2) Effective Intervention: Inhibition of SPP1 in macrophages shows potential for therapeutic intervention, significantly mitigating msi-IDD progression in mouse models.</p> <p>3) Mechanical Stress Insights: Highlights the critical role of mechanical stress in intervertebral disc degeneration, establishing a link between macrophage activity and IDD pathogenesis through advanced molecular profiling.</p> <p></p>

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Deciphering SPP1-related macrophage signaling in the pathogenesis of intervertebral disc degeneration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月18日

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  • Xiao-Jun Yu,
  • Peng Zou,
  • Tian-Qi Li,
  • Xiao-Fan Bai,
  • Shan-Xi Wang,
  • Jian-Bin Guan,
  • Yuan-Ting Zhao,
  • Meng-wei Li,
  • Xiaodong Wang,
  • Ying-guang Wang,
  • Ding-Jun Hao

摘要

This study delved into the molecular mechanisms underlying mechanical stress-induced intervertebral disc degeneration (msi-IDD) through single-cell and high-throughput transcriptome sequencing in mouse models and patient samples. Results exhibited an upsurge in macrophage presence in msi-IDD intervertebral disc (IVD) tissues, with secreted phosphoprotein 1 (SPP1) identified as a pivotal driver exacerbating degeneration via the protein kinase RNA-like endoplasmic reticulum kinase/ activating transcription factor 4/ interleukin-10 (PERK/ATF4/IL-10) signaling axis. Inhibition of SPP1 demonstrated promising outcomes in mitigating msi-IDD progression in both in vitro and in vivo models. These findings underscore the therapeutic promise associated with the modulation of the PERK signaling pathway in IDD, shedding light on the pathogenesis of msi-IDD and proposing a promising avenue for intervention strategies.

Graphical abstract

1) Macrophage Regulation in IDD: SPP1 activates the PERK/ATF4/IL-10 signaling axis in macrophages, increasing IL-10 production, essential for inhibiting msi-IDD progression.

2) Effective Intervention: Inhibition of SPP1 in macrophages shows potential for therapeutic intervention, significantly mitigating msi-IDD progression in mouse models.

3) Mechanical Stress Insights: Highlights the critical role of mechanical stress in intervertebral disc degeneration, establishing a link between macrophage activity and IDD pathogenesis through advanced molecular profiling.