Lee Donghee, Greer Sydney E, Dudley Andrew T
Department of Genetics, Cell Biology and Anatomy and Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Sci Adv. 2025 May 2;11(18):eado6644. doi: 10.1126/sciadv.ado6644.
Physical properties of cartilage are conferred by the composition and ultrastructure of the extracellular matrix. This study focuses on the development of the pericellular matrix (PCM), a domain that directly contacts the chondrocyte and is a key regulator of biomechanical and biochemical signaling. Using three-dimensional cell culture, microfluidic cell compression platforms, and genetic mouse models, we demonstrated that collagen VI is initially assembled at the cell surface and then displaced to form a shell at the PCM-territorial matrix boundary. Cell surface-bound hyaluronan is crucial for the assembly process, and hyaluronan-aggrecan complexes drive displacement. Integrin adhesion is not required early but is crucial to determine the final placement of the collagen VI shell. Dynamic compression accelerated PCM maturation except in aggrecan mutants. Together, these findings provide key insights into the development of the mechanosensitive PCM and establish an in vitro platform to support studies of matrix biology in normal and disease models.
软骨的物理特性由细胞外基质的组成和超微结构赋予。本研究聚焦于细胞周基质（PCM）的发育，该区域直接与软骨细胞接触，是生物力学和生化信号的关键调节因子。利用三维细胞培养、微流控细胞压缩平台和基因小鼠模型，我们证明胶原蛋白VI最初在细胞表面组装，然后移位至PCM-区域基质边界形成一层外壳。细胞表面结合的透明质酸对组装过程至关重要，且透明质酸-聚集蛋白聚糖复合物驱动移位。整合素黏附在早期并非必需，但对于确定胶原蛋白VI外壳的最终位置至关重要。动态压缩加速了PCM的成熟，除了在聚集蛋白聚糖突变体中。总之，这些发现为机械敏感的PCM的发育提供了关键见解，并建立了一个体外平台，以支持对正常和疾病模型中基质生物学的研究。
