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Gallium nitrate regulates rat osteoblast expression of osteocalcin protein and mRNA levels
Author(s) -
Guidon Peter T.,
Salvatori Roberto,
Bockman Richard S.
Publication year - 1993
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650080113
Subject(s) - osteocalcin , osteopontin , osteoblast , medicine , endocrinology , microbiology and biotechnology , chemistry , messenger rna , gene expression , biology , alkaline phosphatase , biochemistry , gene , in vitro , enzyme
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 D 3 ‐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 D 3 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 β 1 (TGFβ 1 ); however, TGF‐β 1 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.