Chondrocytes and Fibrochondrocytes Differentially Process Aggrecan During De Novo Extracellular Matrix Assembly
The material properties of articular cartilage and meniscal fibrocartilage depend on the composition and ultrastructure of the extracellular matrix (ECM). Aggrecan is the predominant large proteoglycan in these tissues, and confers compressive stiffness through immobilization of negatively charged sulfated glycosaminoglycans (sGAG). The abundance of sGAG is in part regulated by cell-mediated proteolysis of the aggrecan core protein, and transforming growth factor-β (TGF-β) family cytokines upregulate aggrecan synthesis in chondrocytes and fibrochondrocytes. The function(s) of aggrecan and mechanisms of aggrecan processing in the meniscus, however, are not well understood. The objective of this study was to examine tissue-specific kinetics and mechanisms of TGF-β-induced aggrecan turnover using the cell-agarose culture system. In addition, the tissue-specific functional implications of increased proteoglycan production were evaluated in terms of construct material properties.