Wilson Christopher G, Nishimuta James F, Levenston Marc E
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Tissue Eng Part A. 2009 Jul;15(7):1513-22. doi: 10.1089/ten.tea.2008.0106.
Aggrecan is an extracellular matrix molecule that contributes to the mechanical properties of articular cartilage and meniscal fibrocartilage, but the abundance and processing of aggrecan in these tissues are different. The objective of this study was to compare patterns of aggrecan processing by chondrocytes and meniscal fibrochondrocytes in tissue explants and cell-agarose constructs. The effects of transforming growth factor-beta 1 (TGF-beta1) stimulation on aggrecan deposition and processing were examined, and construct mechanical properties were measured. Fibrochondrocytes synthesized and retained less proteoglycans than did chondrocytes in tissue explants and agarose constructs. In chondrocyte constructs, TGF-beta1 induced the accumulation of a 120-kDa aggrecan species previously detected in mature bovine cartilage. Fibrochondrocyte-seeded constructs contained high-molecular-weight aggrecan but lacked aggrecanase-generated fragments found in native, immature meniscus. In addition, reflecting the lesser matrix accumulation, fibrochondrocyte constructs had significantly lower compression moduli than did chondrocyte constructs. These cell type-specific differences in aggrecan synthesis, retention, and processing may have implications for the development of functional engineered tissue grafts.
聚集蛋白聚糖是一种细胞外基质分子,它对关节软骨和半月板纤维软骨的力学性能有贡献,但聚集蛋白聚糖在这些组织中的丰度和加工情况有所不同。本研究的目的是比较组织外植体和细胞琼脂糖构建物中软骨细胞和半月板纤维软骨细胞对聚集蛋白聚糖的加工模式。研究了转化生长因子-β1(TGF-β1)刺激对聚集蛋白聚糖沉积和加工的影响,并测量了构建物的力学性能。在组织外植体和琼脂糖构建物中,纤维软骨细胞合成和保留的蛋白聚糖比软骨细胞少。在软骨细胞构建物中,TGF-β1诱导了先前在成熟牛软骨中检测到的120 kDa聚集蛋白聚糖物种的积累。接种纤维软骨细胞的构建物含有高分子量的聚集蛋白聚糖,但缺乏天然未成熟半月板中发现的聚集蛋白聚糖酶产生的片段。此外,由于基质积累较少,纤维软骨细胞构建物的压缩模量明显低于软骨细胞构建物。聚集蛋白聚糖合成、保留和加工方面的这些细胞类型特异性差异可能对功能性工程组织移植物的开发有影响。