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
{"title":"ROCK-dependent mechanotransduction of macroscale forces drives fibrosis in degenerative spinal disease","authors":"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","doi":"10.1038/s41551-025-01396-7","DOIUrl":null,"url":null,"abstract":"<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>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"36 1","pages":""},"PeriodicalIF":26.8000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Biomedical Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1038/s41551-025-01396-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.
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