Gallium nitrate regulates rat osteoblast expression of osteocalcin protein and mRNA levels

Authors

  • Peter T. Guidon Jr.,

    1. Hospital for Special Surgery, New York, New York
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  • Roberto Salvatori,

    1. Department of Medicine, Cornell University Medical College-New York Hospital, New York, New York
    Current affiliation:
    1. University of Chieti, Department of Endocrinology, Chieti, Italy
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  • Richard S. Bockman

    Corresponding author
    1. Hospital for Special Surgery, New York, New York
    2. Department of Medicine, Cornell University Medical College-New York Hospital, New York, New York
    • Hospital for Special Surgery and Cornell University Medical Center 535 East 70th Street New York, NY 10021
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Abstract

Gallium nitrate, a group IIIa metal salt, has been found to be clinically effective for the treatment of accelerated bone resorption in cancer-related hypercalcemia and Paget's disease. Here we report the effects of gallium nitrate on osteocalcin mRNA and protein levels on the rat osteoblast-like cell line ROS 17/2.8. Gallium nitrate reduced both constitutive and vitamin D3-stimulated osteocalcin protein levels in culture medium by one-half and osteocalcin mRNA levels to one-third to one-tenth of control. Gallium nitrate also inhibited vitamin D3 stimulation of osteocalcin and osteopontin mRNA levels but did not affect constitutive osteopontin mRNA levels. Among several different metals examined, gallium was unique in its ability to reduce osteocalcin mRNA levels without decreasing levels of other mRNAs synthesized by ROS 17/2.8 cells. The effects of gallium nitrate on osteocalcin mRNA and protein synthesis mimic those seen when ROS 17/2.8 cells are exposed to transforming growth factor β1 (TGFβ1); however, TGF-β1 was not detected in gallium nitratetreated ROS 17/2.8 cell media. Use of the RNA polymerase II inhibitor 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole demonstrated that gallium nitrate did not alter the stability of osteocalcin mRNA. Transient transfection assays using the rat osteocalcin promoter linked to the bacterial reporter gene chloramphenicol acetyltransferase indicated that gallium nitrate blocked reporter gene expression stimulated by the osteocalcin promoter. This is the first reported effect of gallium nitrate on isolated osteoblast cells.

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