EXPRESSION OF A STABLE ARTICULAR-CARTILAGE PHENOTYPE WITHOUT EVIDENCEOF HYPERTROPHY BY ADULT HUMAN ARTICULAR CHONDROCYTES IN-VITRO

Chondrocytes that were isolated from adult human articular cartilage c hanged phenotype during monolayer tissue culture, as characterized by a fibroblastic morphology and cellular proliferation. Increased prolif eration was accompanied by downregulation of the cartilage-specific ex tracellular matrix proteoglycan, aggrecan, by cessation of type-II col lagen expression, and by upregulation of type-I collagen and versican. This phenomenon observed in monolayer was reversible after the transf er of cells to a suspension culture system. The transfer of chondrocyt es to suspension culture in alginate beads resulted in the rapid upreg ulation of aggrecan and type-II collagen and the downregulation of exp ression of versican and type-I collagen. Type-X collagen and osteopont in, markers of chondrocyte hypertrophy and commitment to endochondral ossification, were not expressed by adult articular chondrocytes cultu red in alginate, even after 5 months. In contrast, type-X collagen was expressed within 2 weeks in a population of cells derived from a feta l growth plate. The inability of adult articular chondrocytes to expre ss markers of chondrocyte hypertrophy has underscored the fundamental distinction between the differentiation pathways that lead to articula r cartilage or to bone. Adult articular chondrocytes expressed only hy aline articular cartilage markers without evidence of hypertrophy.