Friedman Ryan M, Breuninger Arielle S, Aronson Matthew R, Brown Elizabeth A, Patel Neil, Han Lin, Zur Karen B, Gottardi Riccardo
Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Department of Surgery, Division of Otolaryngology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Connect Tissue Res. 2024 Nov;65(6):472-485. doi: 10.1080/03008207.2024.2435364. Epub 2024 Dec 12.
The vocal folds (VFs) are among the most mechanically active connective tissues, vibrating between 80 and 250 hz during speech. Overall VF function is determined by the composition and structure of their extracellular matrix (ECM). During tissue maturation, the VFs remodel from a monolayer of collagen fibers to a tri-layered structure, affecting tissue biomechanics. However, age-related VF ECM remodeling remains poorly understood since few studies have explored the proteins governing collagen fibrillogenesis or the non-collagenous ECM components critical for VF elasticity.
VFs from immature, sexually mature, and skeletally mature rats were evaluated by endoscopy, histology, and electron microscopy for cellular and biochemical composition, ECM organization, and proteoglycan distribution. Nanoindentation modulus was determined by atomic force microscopy.
Collagen fiber abundance, maturity, and alignment are low in immature rats but show an age-dependent increase during tissue maturation. Lumican and fibromodulin, which regulate early-stage collagen fibril formation, are distributed throughout the VFs, and their abundance decreases with age. Decorin, involved in collagen organization, is concentrated just beneath the epithelium and increases with age. Elastin levels increase during tissue maturation, but hyaluronic acid abundance and distribution remain consistent with age. VF nanoindentation modulus trends toward a decrease with age.
This work identifies changes in VF ECM composition and organization during tissue maturation, focusing on proteins that regulate collagen fibrillogenesis, fiber assembly, and VF biomechanics. These findings may inform the development of pro-reparative therapies designed to influence collagen network structure and overall ECM dysregulation in a number of laryngeal pathologies.
声带是机械活性最强的结缔组织之一，在说话时以80至250赫兹的频率振动。声带的整体功能由其细胞外基质（ECM）的组成和结构决定。在组织成熟过程中，声带从单层胶原纤维重塑为三层结构，影响组织生物力学。然而，由于很少有研究探讨控制胶原纤维形成的蛋白质或对声带弹性至关重要的非胶原ECM成分，与年龄相关的声带ECM重塑仍知之甚少。
通过内窥镜检查、组织学和电子显微镜对未成熟、性成熟和骨骼成熟大鼠的声带进行评估，以确定细胞和生化组成、ECM组织和蛋白聚糖分布。通过原子力显微镜测定纳米压痕模量。
未成熟大鼠的胶原纤维丰度、成熟度和排列程度较低，但在组织成熟过程中呈年龄依赖性增加。调节早期胶原纤维形成的核纤蛋白和纤调蛋白分布于整个声带，其丰度随年龄增长而降低。参与胶原组织形成的核心蛋白聚糖集中在上皮下方，并随年龄增长而增加。弹性蛋白水平在组织成熟过程中增加，但透明质酸的丰度和分布随年龄保持一致。声带纳米压痕模量随年龄呈下降趋势。
本研究确定了组织成熟过程中声带ECM组成和组织的变化，重点关注调节胶原纤维形成、纤维组装和声带生物力学的蛋白质。这些发现可能为旨在影响多种喉部疾病中胶原网络结构和整体ECM失调的促修复疗法的开发提供信息。
