2. Academic Validation
  3. Deciphering SPP1-related macrophage signaling in the pathogenesis of intervertebral disc degeneration

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

  • Cell Biol Toxicol. 2025 Jan 18;41(1):33. doi: 10.1007/s10565-024-09948-4.
Xiao-Jun Yu # 1 2,  Peng Zou # 1 2,  Tian-Qi Li 1 2,  Xiao-Fan Bai 1 2,  Shan-Xi Wang 1 2,  Jian-Bin Guan 1 2,  Yuan-Ting Zhao 1 2,  Meng-Wei Li 3,  Xiaodong Wang 1 2,  Ying-Guang Wang 4 5,  Ding-Jun Hao 6 7
Affiliations

Affiliations

  • 1 Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, No.555 Friendship East Road, South Gate, Beilin District, Xi'an, 710054, Shaanxi, China.
  • 2 Shaanxi Key Laboratory of Spine Bionic Treatment, No.555 Friendship East Road, South Gate, Beilin District, Xi'an, Shaanxi, China.
  • 3 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 4 Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, No.555 Friendship East Road, South Gate, Beilin District, Xi'an, 710054, Shaanxi, China. d202082001@hust.edu.cn.
  • 5 Shaanxi Key Laboratory of Spine Bionic Treatment, No.555 Friendship East Road, South Gate, Beilin District, Xi'an, Shaanxi, China. d202082001@hust.edu.cn.
  • 6 Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, No.555 Friendship East Road, South Gate, Beilin District, Xi'an, 710054, Shaanxi, China. haodingjun@mail.xjtu.edu.cn.
  • 7 Shaanxi Key Laboratory of Spine Bionic Treatment, No.555 Friendship East Road, South Gate, Beilin District, Xi'an, Shaanxi, China. haodingjun@mail.xjtu.edu.cn.
  • # Contributed equally.
PMID: 39825191 DOI: 10.1007/s10565-024-09948-4
Abstract

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.

Keywords

Intervertebral disc degeneration; Macrophages; Mechanical stress; PERK signaling pathway; SPP1; Targeted intervention.

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