2. Academic Validation
  3. Thrombin induces degradation of murine intervertebral discs via angiogenesis and M1-like polarization of macrophages

Thrombin induces degradation of murine intervertebral discs via angiogenesis and M1-like polarization of macrophages

  • Sci Rep. 2025 Oct 6;15(1):34817. doi: 10.1038/s41598-025-18684-6.
Rikito Tatsuno 1,  Takashi Ando 2 3,  Taro Fujimaki 1,  Yoshihiro Takayama 4,  Tetsuro Ohba 1,  Hirotaka Haro 1
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
  • 2 Department of Orthopedic Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan. [email protected].
  • 3 Department of Rehabilitation, Koshu Rehabilitation Hospital, Yamanashi, Japan. [email protected].
  • 4 Department of Orthopedic Surgery, Yamanashi Kosei Hospital, Yamanashi, Japan.
PMID: 41053148 DOI: 10.1038/s41598-025-18684-6
Abstract

With the marked aging of the global population, the prevalence of musculoskeletal disorders due to low back pain has escalated, with an associated increase in the number of individuals requiring nursing care. To help identify novel therapies for treating disc degeneration, we examined the roles of Thrombin and macrophages in intervertebral disc degeneration, a significant cause of low back pain. Experiments using a needle-puncture mouse tail model of disc degeneration confirmed that this process led to the production of Thrombin and MCP-1. Thrombin altered macrophage markers, increasing the population of M1 markers and decreasing that of M2 markers. Therefore, increased Thrombin and MCP-1 production may induce disc degeneration by inducing M1-type polarization of migrated macrophages. Disc tissue M1-macrophage levels were elevated 3 weeks after puncture. Administering SCH79797, a Thrombin receptor (PAR1) antagonist, suppressed thrombin-induced disc degeneration and inhibited macrophage migration, M1 polarization, VEGF production, and angiogenesis. These findings suggest that the suppression of Thrombin function in intervertebral disc inflammation is a novel and promising approach for treating disc degeneration.

Keywords

Angiogenesis; Disc degeneration; Low back pain; Macrophage polarization; Thrombin.

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