Chondrocytes and meniscal fibrochondrocytes differentially process aggrecan during de novo extracellular matrix assembly.

Abstract

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.