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<p>Chronic repetitive forces on the spinal column promote the development of degenerative spinal disease. Yet the mechanisms linking such macroscale mechanical forces to tissue hypertrophy remain unknown. Here we show that fibrotic regions in human ligamentum flavum naturally exposed to high stress display elevated Rho-associated kinase (ROCK) signalling and an increased density of myofibroblasts expressing smooth muscle actin α. The myofibroblasts were localized in regions of elevated stiffness and microstress, such accumulation was ROCK dependent, and ROCK inhibition partially reduced the stress-driven transcriptional responses. Our findings support the further investigation of ROCK inhibitors for the treatment of degenerative spinal disease.</p>

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ROCK-dependent mechanotransduction of macroscale forces drives fibrosis in degenerative spinal disease

  • 期刊论文

  • 发表日期：

    2025年5月29日

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  • Muhamed Hadzipasic,
  • Margaret S. Sten,
  • Elie Massaad,
  • Ali Kiapour,
  • Ian D. Connolly,
  • Eric Esposito,
  • Ryan Burns,
  • George Nageeb,
  • Muneeb A. Sharif,
  • Joseph Bradley,
  • Leland Richardson,
  • Sami Shaikh,
  • Bryan D. Choi,
  • Gunnlaugur P. Nielsen,
  • Jean-Valery C. Coumans,
  • Lawrence F. Borges,
  • John H. Shin,
  • Alan J. Grodzinsky,
  • Hadi T. Nia,
  • Ganesh M. Shankar

摘要

Chronic repetitive forces on the spinal column promote the development of degenerative spinal disease. Yet the mechanisms linking such macroscale mechanical forces to tissue hypertrophy remain unknown. Here we show that fibrotic regions in human ligamentum flavum naturally exposed to high stress display elevated Rho-associated kinase (ROCK) signalling and an increased density of myofibroblasts expressing smooth muscle actin α. The myofibroblasts were localized in regions of elevated stiffness and microstress, such accumulation was ROCK dependent, and ROCK inhibition partially reduced the stress-driven transcriptional responses. Our findings support the further investigation of ROCK inhibitors for the treatment of degenerative spinal disease.