Decorin Regulates the Aggrecan Network Integrity and Biomechanical Functions of Cartilage Extracellular Matrix
Decorin Regulates the Aggrecan Network Integrity and Biomechanical Functions of Cartilage Extracellular Matrix
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DOI：
10.1021/acsnano.9b04477
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发表时间：
2019-10-01
期刊：
影响因子：
17.1
通讯作者：
Han, Lin
中科院分区：
文献类型：
--
作者：
Han, Biao;Li, Qing;Han, Lin
关节生物力学功能依赖于软骨细胞外基质的完整性。了解支配软骨基质组装的分子活性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（一种富含亮氨酸的蛋白聚糖）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，我们发现软骨基质的主要蛋白聚糖聚集蛋白聚糖含量显著降低，胶原纤维纳米结构发生轻微变化。聚集蛋白聚糖的这种损失导致软骨的生物力学性质显著受损，包括模量降低、透水性升高和能量耗散能力降低。在细胞水平上，我们发现核心蛋白聚糖的功能是增加聚集蛋白聚糖在软骨细胞新基质中的保留，而不是直接影响聚集蛋白聚糖的生物合成。在分子水平上，我们证明了核心蛋白聚糖显著增加聚集蛋白聚糖和聚集蛋白聚糖分子之间以及聚集蛋白聚糖分子和胶原蛋白II原纤维之间的粘附。我们假设核心蛋白聚糖在介导软骨的基质完整性和生物力学功能中起着至关重要的结构作用，通过提供物理连接来增加聚集蛋白聚糖分子在纳米级的粘附和组装。
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 20 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.