Effect of gallium nitrate in vitro and in normal rats.
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.
Jenis
L G
LG
Department of Orthopedics, University of Massachusetts Medical Center, Worcester, Massachusetts 01655.
Waud
C E
CE
Stein
G S
GS
Lian
J B
JB
Baran
D T
DT
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D005260:Female; D005708:Gallium / Q000494:pharmacology*; D015870:Gene Expression; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D012016:Reference Values; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D015675:Osteocalcin; D003094:Collagen; D005708:Gallium; C027235:gallium nitrate