Effect of gallium nitrate in vitro and in normal rats
Department of Medicine; Department of Cell Biology
Animals; Bone Density; Bone Development; Cell Differentiation; Cell Division; Cells, Cultured; Collagen; Female; Gallium; Gene Expression; Osteoblasts; Osteocalcin; RNA, Messenger; Random Allocation; Rats; Reference Values; Tumor Cells, Cultured
Gallium nitrate (GN) is an inhibitor of bone resorption and thereby may result in a change in coupled bone formation. In the present investigation the effects of GN on bone formation were studied in the rat osteosarcoma (ROS) 17/2.8 cell line and normal diploid rat osteoblasts (ROB) in vitro and the femur of rats treated in vivo, measuring mRNA levels for two osteoblast parameters, type I collagen, a marker of matrix formation, and osteocalcin, a bone specific protein and also histone H4, a marker of cell proliferation. GN, at 50 microM for 3 h, increased type I collagen mRNA levels by 132% in ROS 17/2.8 cells and by 122% in proliferating ROB cells. Osteocalcin (OC) mRNA levels were decreased by 61% in ROS 17/2.8 cells and by 97% in differentiated ROB cells. These changes occurred in the absence of any effects on cell proliferation. Seventy-day-old female rats were then treated with GN, 0.5 mg/kg/day, for 3 weeks. As previously reported, GN decreased serum calcium levels, but had no effect on lumbar or femoral bone density. In contrast to the in vitro effects, GN had no effect on type I collagen steady-state mRNA levels in the femur; however, it decreased OC steady-state mRNA levels in the femur by 58%. These results suggest that GN has similar in vitro effects in transformed and normal osteoblasts, while the collagen-stimulatory effects observed in vitro cannot be extrapolated to in vivo models. The consistent inhibition of osteocalcin in vitro and in vivo suggests a more specific target for GN that may relate to its effects in inhibiting bone resorption in normal rats.
DOI of Published Version
J Cell Biochem. 1993 Jul;52(3):330-6. Link to article on publisher's site
Journal of cellular biochemistry
Jenis LG, Waud CE, Stein GS, Lian JB, Baran DT. (1993). Effect of gallium nitrate in vitro and in normal rats. Stein, Stein, Lian, vanWijnen Lab Publications. https://doi.org/10.1002/jcb.240520309. Retrieved from https://escholarship.umassmed.edu/stein/100