Fluoroquinolone's effect on growth of human chondrocytes and chondrosarcomas - In vitro and in vivo correlation

Clinical and in vitro studies have demonstrated that fluoroquinolones are t oxic to chondrocytes; however, the exact mechanism of fluoroquinolone arthr opathy is unknown. We investigated the toxicity of ciprofloxacin on normal cartilage and on cartilaginous tumors. Normal human cartilage, enchondroma, and chondrosarcoma explants were cultured either alone or with the additio n of ciprofloxacin at 1, 10, or 20 mg/L of medium. Samples were collected u p to twenty-one days after treatment and were processed for electron micros copy and conventional light microscopy. The specimens were characterized mo rphologically with use of conventional light microscopy, electron microscop y, and immunohistochemistry to identify extracellular matrix, cell prolifer ation, and apoptosis. Cultures of normal chondrocytes expressed type-II collagen. Electron micros copy revealed a large amount of glycogen in the cells; the presence of fat droplets, rough endoplasmic reticulum, and prominent Golgi apparatus; and a proteoglycan layer surrounding the cells. With prolonged ciprofloxacin tre atment and with increased doses, there was an increase in dilated rough end oplasmic reticulum, the appearance of phagosomes, and disintegrated bundles of vimentin filaments. The treated chondrocytes showed a decrease in cell proliferation, but there was no induction of apoptosis or effect on the exp ression of extracellular matrix proteins. Ciprofloxacin-treated chondrosarc oma cultures and tissue samples showed changes in cartilage matrix composit ion. Ultrastructural analysis demonstrated clumped glycogen, dilation of en doplasmic reticulum, numerous abnormal lysosomes containing degeneration pr oducts, and a decreased proteoglycan deposit surrounding the tumor cells. T reated chondrosarcoma cells and tissue specimens did not proliferate, and a poptosis was induced. In contrast, the in vitro growth of other noncartilag inous malignant tumors like osteosarcoma and liposarcoma was unaffected by ciprofloxacin. Our results indicate that ciprofloxacin is toxic to chondrocytes. In vitro and in vivo treated chondrosarcomas are the most affected.