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Calcified tissue international

Effects of thionaphthene 2-carboxylic acid and related compounds on bone resorption in organ culture.


PMID 2998577

Abstract

We have compared the effects of thiophene 2-carboxylic acid (TCA) and a number of sulfur- and nitrogen-containing analogs for their ability to inhibit bone resorption in organ cultures of fetal rat long bones. Four compounds,--thionaphthene-2-carboxylic acid (TNCA), dibenzo-thiophene-4-carboxylic acid, indole-2-carboxylic acid and carbazole-1-carboxylic acid--caused a dose-related inhibition of PTH-stimulated bone resorption, although TCA was ineffective in this system. TNCA at 3 X 10(-4) M or 10(-4) M was the most potent inhibitor of PTH-stimulated bone resorption and was selected for further study. TNCA also inhibited stimulation of resorption by prostaglandin E2 and 1,25-dihydroxyvitamin D. Unlike calcitonin, the effect of TNCA was persistent and did not show escape. Moreover, TNCA could inhibit resorption in bones that had previously escaped from calcitonin. TNCA did not appear to be a nonspecific toxin, since it did not decrease incorporation of [3H]thymidine or [3H]proline into fetal rat long bones. The fact that resorption in unstimulated cultures was only decreased when the control rates were high also argues against nonspecific toxicity. Moreover, this suggests that TNCA will be most effective under conditions of accelerated bone resorption when an inhibiting effect is most desirable.

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