School of Biomedical Engineering, Science and Health Systems , Drexel University , Philadelphia , Pennsylvania 19104 , United States.
Department of Molecular Pharmacology and Physiology, Morsani School of Medicine , University of South Florida , Tampa , Florida 33612 , United States.
ACS Nano. 2019 Oct 22;13(10):11320-11333. doi: 10.1021/acsnano.9b04477. Epub 2019 Oct 1.
Joint biomechanical functions rely on the integrity of cartilage extracellular matrix. Understanding the molecular activities that govern cartilage matrix assembly is critical for developing effective cartilage regeneration strategies. This study elucidated the role of decorin, a small leucine-rich proteoglycan, in the structure and biomechanical functions of cartilage. In decorin-null cartilage, we discovered a substantial reduction of aggrecan content, the major proteoglycan of cartilage matrix, and mild changes in collagen fibril nanostructure. This loss of aggrecan resulted in significantly impaired biomechanical properties of cartilage, including decreased modulus, elevated hydraulic permeability, and reduced energy dissipation capabilities. At the cellular level, we found that decorin functions to increase the retention of aggrecan in the neo-matrix of chondrocytes, rather than to directly influence the biosynthesis of aggrecan. At the molecular level, we demonstrated that decorin significantly increases the adhesion between aggrecan and aggrecan molecules and between aggrecan molecules and collagen II fibrils. We hypothesize that decorin plays a crucial structural role in mediating the matrix integrity and biomechanical functions of cartilage by providing physical linkages to increase the adhesion and assembly of aggrecan molecules at the nanoscale.
关节生物力学功能依赖于软骨细胞外基质的完整性。了解调控软骨基质组装的分子活动对于开发有效的软骨再生策略至关重要。本研究阐明了核心蛋白聚糖（decorin）在软骨结构和生物力学功能中的作用。在核心蛋白聚糖缺失的软骨中，我们发现软骨基质中主要的蛋白聚糖聚集蛋白聚糖（aggrecan）的含量显著减少，胶原纤维纳米结构有轻微改变。聚集蛋白聚糖的丢失导致软骨的生物力学性能显著受损，包括弹性模量降低、水力渗透性增加以及能量耗散能力降低。在细胞水平上，我们发现核心蛋白聚糖的功能是增加软骨细胞新基质中聚集蛋白聚糖的保留，而不是直接影响聚集蛋白聚糖的生物合成。在分子水平上，我们证明核心蛋白聚糖显著增加了聚集蛋白聚糖与聚集蛋白聚糖分子之间以及聚集蛋白聚糖分子与 II 型胶原纤维之间的黏附。我们假设核心蛋白聚糖通过提供物理连接，在纳米尺度上增加聚集蛋白聚糖分子的黏附与组装，从而在介导软骨基质完整性和生物力学功能方面发挥关键的结构作用。
