The Effect and Mode of Action of Tetracycline on Bone Development in Vitro

Abstract

Antibiotics of the tetracycline group are known to pass the placental barrier in both experimental animals and man (1,2), and to become selectively incorporated into the developing fetal skeleton (3,4). Moreover, these antibiotics have been reported to interfere with the mineralization of fetal bone and teeth, and so lead to growth retardation and hypoplasia of the enamel (5,6,7). Yet the mode of action of the drugs is unknown and one can speculate on a variety of target sites in the chain of events, starting with determination and proliferation of the chondroblasts and ending with the formation of bone mineral (7). To analyze these questions, an in vitro method was applied for several reasons: in vivo experiments of classic type are hampered by a variety of difficulties. The role of the placental barrier is not fully understood, the pharmacokinetics of tetracycline in various experimental animals is not clarified, and the sensitive period of the drug is not known. In an organotypic culture of fetal bones at least some of these difficulties could, as we believe, be avoided.