Naha Ananya, Sorensen John, Lazarte Santiago, Joshi Sailesti, Driscoll Tristan P
Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Tallahassee, FL, 32310, USA.
Adv Biol (Weinh). 2025 Jul 27:e00315. doi: 10.1002/adbi.202500315.
Degenerative disc disease is strongly associated with low back pain, making it a leading cause of disability. With injury and age, cellular remodeling of the disc tissue leads to compositional changes, stiffening, and loss of stress relaxation, particularly in the central gelatinous nucleus pulposus (NP) region of the disc. As part of this extracellular matrix (ECM) remodeling, there is an increase in the deposition of fibronectin, a strongly adhesive integrin ligand that is known to regulate inflammatory signaling. However, it is unclear how these pathological changes in cellular adhesion regulate cell phenotype, and which domains of fibronectin are specifically involved. Here, a dextran vinyl sulfone (DexVS) hydrogel system is employed for presentation of specific fibronectin domains. Fibronectin peptides are found to enhance YAP signaling, inflammatory NF-κB signaling, cellular adhesion, and cellular contractility in NP cells, which leads to a decrease in aggrecan gene expression. Covalent modification of these DexVS hydrogels with bioactive peptides allows for targeted interactions with specific integrin receptors that are involved in healthy or degenerative signaling. In doing so, the integrin binding peptides from fibronectin are identified to activate a contractile phenotype in NP cells.
椎间盘退变与腰背痛密切相关，是导致残疾的主要原因。随着损伤和年龄增长，椎间盘组织的细胞重塑会导致成分改变、僵硬以及应力松弛丧失，尤其是在椎间盘中央的胶状髓核（NP）区域。作为这种细胞外基质（ECM）重塑的一部分，纤连蛋白的沉积增加，纤连蛋白是一种强粘附性整合素配体，已知其可调节炎症信号。然而，尚不清楚细胞粘附中的这些病理变化如何调节细胞表型，以及纤连蛋白的哪些结构域具体参与其中。在此，采用葡聚糖乙烯砜（DexVS）水凝胶系统来呈现特定的纤连蛋白结构域。研究发现，纤连蛋白肽可增强NP细胞中的YAP信号、炎症性NF-κB信号、细胞粘附和细胞收缩力，这会导致聚集蛋白聚糖基因表达降低。用生物活性肽对这些DexVS水凝胶进行共价修饰，可实现与参与健康或退变信号传导的特定整合素受体的靶向相互作用。通过这样做，已确定来自纤连蛋白的整合素结合肽可激活NP细胞中的收缩表型。
