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Gallium nitrate increases type I collagen and fibronectin mRNA and collagen protein levels in bone and fibroblast cells

Authors

  • Richard S. Bockman,

    Corresponding author
    1. The Hospital for Special Surgery and Cornell University Medical College, New York, New York 10021
    • The Hospital for Special Surgery and Cornell University Medical College, 535 East 70th Street, New York, NY 10021
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  • Peter T. Guidon Jr.,

    1. The Hospital for Special Surgery and Cornell University Medical College, New York, New York 10021
    Current affiliation:
    1. Seton Hall University, South Orange, NJ 07079
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  • Lydia C. Pan,

    1. The Hospital for Special Surgery and Cornell University Medical College, New York, New York 10021
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  • Roberto Salvatori,

    1. The Hospital for Special Surgery and Cornell University Medical College, New York, New York 10021
    Current affiliation:
    1. University of Connecticut Health Center, Farmington, CT 06032
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  • Alan Kawaguchi

    1. The Hospital for Special Surgery and Cornell University Medical College, New York, New York 10021
    Current affiliation:
    1. New York University Medical School, New York, NY 10016
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Abstract

Gallium is a Group IIIa transitional element with therapeutic efficacy in the treatment of metabolic bone disorders. Previously described antiresorptive effects of gallium on osteoclasts are not sufficient to account for the full range of effects of gallium on bone structure and metabolism. We have recently shown that gallium nitrate inhibits osteocalcin gene expression and the synthesis of osteocalcin protein, an osteoblast-specific bone matrix protein that is though to serve as a signal 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 fibroblastic cells. Rat calvarial explants exposed to gallium nitrate for 48 h showed increased incorporation of 3H-proline into hydroxyproline and collagenase digestible protein. In addition, gallium treatment increased steady-state mRNA levels for fibronectin and type I procollagen chains in primary rat calvarial osteoblast-enriched cultures, the ROS 17/2.8 osteoblastic osteosarcoma line, and nontransformed human dermal fibroblasts. These findings suggest that the exposure of mesenchymally-derived cells to gallium results in an altered pattern of matrix protein synthesis that would favor increased bone formation.

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