Effect of tetracycline on osteogenesis in vitro

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Abstract
The effect of tetracycline on developing bones was explored in organotypic tissue culture. Such culture conditions proved to be suitable for certain experiments dealing with the “teratogenic” effect of drugs, and the first part of the paper examines the possibilities, limitations and fallacies of this technique.Embryonic mouse bones cultivated in vitro show rapid incorporation of tetracycline, and after 30 minutes of cultivation a definite fluorescence is seen. The drug is incorporated at least into two fractions: one which is rapidly released after the withdrawal of tetracycline and one which remains in the calcium‐containing zones of the bone.Tetracycline in concentrations of the order of 5 μg/ml completely inhibits the elongation of the calcified zone of the bone rudiments and the increase of their total calcium. However, experiments with labeled calcium still show an incorporation in the presence of tetracycline although no cumulative uptake is seen. The results thus indicate the existence of a rapidly incorporated calcium fraction which is independent of tetracycline.The inhibition of calcification is reversible up to some five days of treatment, whereafter a transfer to normal medium does not lead to a recovery, and the mineralization seems to be irreversibly blocked.It is concluded that the results speak in favor of the theory of a direct action of tetracycline on the formations of the bone salts, rather than interference with enzymatic activity dependent on divalent cations.