Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Tallahassee, Florida, USA.
J Orthop Res. 2024 Feb;42(2):434-442. doi: 10.1002/jor.25670. Epub 2023 Aug 15.
Intervertebral disc degeneration involves the breakdown of the discs of the spine due to genetics, aging, or faulty mechanical loading. As part of the progression of the disease, nucleus pulposus cells lose their phenotypic characteristics, inducing inflammation and extracellular matrix (ECM) alterations that result in a loss of disc mechanical homeostasis. Fibronectin is one ECM molecule that has been shown to be upregulated in disc degeneration and plays an important role in the progression of a wide variety of fibrotic diseases. Fragments of fibronectin have also long been associated with both osteoarthritis and disc degeneration. The goal of this work is to test the effects of fibronectin on disc cell phenotype, mechanosensing, and inflammatory signaling. We identify that fibronectin increases the activation of cellular contractility, the mechanosensitive transcription factor Yes-associated protein, and the inflammatory transcription factor nuclear factor-κB. This results in decreased production and expression of proteoglycans, which are required to maintain healthy disc function. Thus, fibronectin is a potential regulator of phenotypic changes in disc degeneration, and a potential target for treating disc degeneration at the cellular level. Understanding the role of fibronectin, and its potential as a therapeutic target, could provide new approaches for preventing or reversing disc degeneration.
椎间盘退变是由于遗传、衰老或机械负荷不当等因素导致脊柱间盘的破坏。作为疾病进展的一部分，髓核细胞失去其表型特征，引发炎症和细胞外基质（ECM）改变，导致椎间盘力学平衡丧失。纤连蛋白是一种 ECM 分子，在椎间盘退变中被上调，并在多种纤维化疾病的进展中发挥重要作用。纤连蛋白片段也长期以来与骨关节炎和椎间盘退变有关。这项工作的目的是测试纤连蛋白对椎间盘细胞表型、机械感知和炎症信号的影响。我们发现纤连蛋白增加了细胞收缩性的激活、机械敏感转录因子 Yes 相关蛋白和炎症转录因子核因子-κB。这导致蛋白聚糖的产生和表达减少，而蛋白聚糖是维持健康椎间盘功能所必需的。因此，纤连蛋白是椎间盘退变中表型变化的潜在调节剂，也是治疗椎间盘退变的潜在细胞水平靶点。了解纤连蛋白的作用及其作为治疗靶点的潜力，可能为预防或逆转椎间盘退变提供新的方法。
