GALLIUM NITRATE INCREASES TYPE-I COLLAGEN AND FIBRONECTIN MESSENGER-RNA AND COLLAGEN PROTEIN-LEVELS IN BONE AND FIBROBLAST CELLS

Gallium is a Group IIIa transitional element with therapeutic efficacy in the treatment of metabolic bone disorders. Previously described an tiresorptive effects of gallium on osteoclasts are not sufficient to a ccount for the full range of effects of gallium on bone structure and metabolism. We have recently shown that gallium nitrate inhibits osteo calcin gene expression and the synthesis of osteocalcin protein, an os teoblast-specific bone matrix protein that is thought to serve as a si gnal to trigger osteoclastic resorption. Here we present evidence for an additional mechanism by which gallium may function to augment bone mass by altering matrix protein synthesis by osteoblastic and fibrobla stic cells. Rat calvarial explants exposed to gallium nitrate for 48 h showed increased incorporation of H-3-proline into hydroxyproline and collagenase digestible protein. In addition, gallium treatment increa sed steady-state mRNA levels for fibronectin and type I procollagen ch ains in primary rat calvarial osteoblast-enriched cultures, the ROS 17 /2.8 osteoblastic osteosarcoma line, and nontransformed human dermal f ibroblasts. These findings suggest that the exposure of mesenchymally- derived cells to gallium results in an altered pattern of matrix prote in synthesis that would favor increased bone formation. (C) 1993 Wiley -Liss, Inc.