Effects of 1-Hydroxyethylidene-1, 1-Bisphosphonate (HEBP) on the Synthesis of Dentin Matrix Proteins in the Mouse

The drug 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) is known to inhibit the mineralization of bone and dentin. Its mechanism of action, however, has not yet been elucidated. In order to study its effects on dentinogenesis, mice were supplied with either physiological saline or HEBP in a dose of 10 mg P/kg body weight. This dose is known to interfere with the deposition of mineral crystallites in dentin matrix. The animals were then given a combined injection of [³H]-serine and [¹⁴C] -proline (or [¹⁴C]-glycine) and killed 8–9 days thereafter. The dentin proteins were isolated and fractionated in soluble proteins among which phosphoproteins, CNBr-peptides of collagen and collagen-associated phosphoproteins. It was found that HEBP had a strong inhibitory effect on the synthesis of phosphoproteins and to a lesser extent on that of collagen. The inhibition of the formation of these proteins is supposed to be related to the impaired calcification of dentin under the influence of the bisphosphonate.