Effect of gallium nitrate in vitro and in normal rats.

Abstract

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.

• Authors: L G Jenis, C E Waud, G S Stein, J B Lian, D T Baran
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 52 Issue 3 Pg. 330-6 (Jul 1993) ISSN: 0730-2312 [Print] United States
• PMID: 8366144 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• 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