Hadzipasic Muhamed, Sten Margaret S, Massaad Elie, Kiapour Ali, Connolly Ian D, Esposito Eric, Burns Ryan, Nageeb George, Sharif Muneeb A, Bradley Joseph, Richardson Leland, Shaikh Sami, Choi Bryan D, Nielsen Gunnlaugur P, Coumans Jean-Valery C, Borges Lawrence F, Shin John H, Grodzinsky Alan J, Nia Hadi T, Shankar Ganesh M
Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Biomedical Engineering, Boston University, Boston, MA, USA.
Nat Biomed Eng. 2025 May 29. doi: 10.1038/s41551-025-01396-7.
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.
脊柱上的慢性重复作用力会促进退行性脊柱疾病的发展。然而，将这种宏观机械力与组织肥大联系起来的机制仍不清楚。在这里，我们表明，自然暴露于高应力下的人黄韧带中的纤维化区域显示出Rho相关激酶（ROCK）信号升高，以及表达平滑肌肌动蛋白α的肌成纤维细胞密度增加。肌成纤维细胞定位于硬度和微应力升高的区域，这种积累依赖于ROCK，并且ROCK抑制可部分降低应力驱动的转录反应。我们的研究结果支持进一步研究ROCK抑制剂用于治疗退行性脊柱疾病。
