[Human articular chondrocyte culture. Value in pharmacotoxicology]

Inflammatory and degenerative joint diseases are a major health problem of today. Research is aimed at understanding the processes that bring about degeneration and at the pharmacotoxicological studies of new compounds. Articular cartilage is a connective tissue consisting of an organized extracellular matrix, composed of collagen and proteoglycan aggregates, in which chondrocytes are embedded. Chondrocyte culture has been developed since 1971. However, the use of human chondrocytes for pharmacotoxicology studies is much more recent. The effect of agents can be studied on a number of aspects of chondrocyte metabolism. The most studied are: cell proliferation, proteoglycan degradation and release of matrix proteolytic enzymes or cytokines in the culture medium. Several types of chondrocyte culture can be used for in vitro studies. Organ culture of cartilage slices permits investigation on intact tissue. Chondrocytes can also be released from the articular tissue by serial enzymatic digestions and cultured in a monolayer or tridimensional system. Monolayer culture is easy to set up and allows the culture of large amounts of cells. However, this type of culture is hindered by the phenotypic instability of the chondrocytes. Culture in suspension or within a gel (agarose, collagen) or alginate beads is more suitable for the maintenance of the differentiated phenotype. Chondrocyte immortalization by transfection with oncogenes has been described, but the immortalizing agent still needs to be improved to permit the maintenance of some differentiative properties. The most studied agents are non-steroidal anti-inflammatory drugs. Chondroprotective drugs should also be mentioned. The type of chondrocyte culture for pharmacotoxicological study should be chosen keeping in mind the expected goals of the research undertaken.