Integrins mediate the effects of quinolones and magnesium deficiency on cultured rat chondrocytes

Chondrocyte-matrix interaction is mediated by a series of adhesion molecule s. Both alpha and beta integrin subunits are involved and govern crucial fu nctions of cell adhesion and signal transduction. These molecules modulate proliferation and differentiation, thus establishing cartilage integrity. W e studied the influence of magnesium deficiency and quinolone antibiotics ( which form chelate complexes with divalent cations) on chondrocytes in vitr o in order to assess the role of Mg2+ ions in integrin function and to esta blish cellular changes mediated via integrin signal transduction. Mg2+-free medium and quinolone supplementation was found to decrease chondr ocyte attachment to collagen type II-coated coverslips. Adhesion and growth of chondrocytes were reduced in the respective medium. Organisation of cyt oskeletal fibers (vimentin) was changed and formation of stress fibers (f-a ctin) was disturbed. Additionally, rates of cell proliferation declined. Th ese results indicate that quinolone-magnesium complex formation is importan t for chondrotoxicity of these substances. Cell-matrix detachment and morph ological alterations described in vitro may explain the lesions observed in articular cartilage after quinolone administration in vivo. The attachment assay described could serve as a simple test to establish the susceptibili ty of chondrocytes of different species to different quinolones in use or n ew ones to be introduced.