Gadolinium inhibits thymidine incorporation and induces apoptosis in chondrocytes

Magnetic resonance arthrography, a procedure where contrast agents containi ng gadolinium are administered intra-articularly, has become a useful tool in musculoskeletal diagnosis. Although considered safe For systemic use. to xicities in some tissues have been identified for both free gadolinium ion and the gadolinium chelates used as contrast. In this Study the effects of short-term exposure of articular chondrocytes to gadolinium contrast were e xamined by assaying for proteoglycan synthesis. cell proliferation, and apo ptosis. Bovine chondrocytes were grown in monolayer Culture and exposed to gadodiamide for 16 h. Proteoglycan synthesis was measured through incorpora tion of radiolabeled Sulfate. Uptake of radiolabeled thymidine assessed cel l proliferation. Apoptosis was detected using the TUNEL assay, where DNA st rand breaks characteristic of apoptosis are labeled with fluorescent nucleo tide. Proteoglycan synthesis was stimulated by lower dose exposure to gadod iamide. At higher doses, proteoglycan synthesis returned to baseline. Cell proliferation decreased following exposure to gadodiamide in a dose-depende nt manner. Chondrocyte apoptosis was induced in a dose-dependent manner. Fu rther work is needed to determine if these in vitro effects are present in the intact joint. (C) 2001 Orthopaedic Research Society. Published by Elsev ier Science Ltd. All rights reserved.