Effect of gallium nitrate in vitro and in normal rats

J Cell Biochem. 1993 Jul;52(3):330-6. doi: 10.1002/jcb.240520309.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Density / drug effects
  • Bone Development / drug effects
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • Collagen / genetics
  • Female
  • Gallium / pharmacology*
  • Gene Expression
  • Osteoblasts / drug effects*
  • Osteocalcin / genetics
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Reference Values
  • Tumor Cells, Cultured


  • RNA, Messenger
  • Osteocalcin
  • Collagen
  • Gallium
  • gallium nitrate