Interferon-gamma inhibits 1,25-dihydroxyvitamin D3-stimulated synthesis of bone GLA protein in rat osteosarcoma cells by a pretranslational mechanism

Endocrinology
M S NanesB D Catherwood

Abstract

Interferon-gamma (IFN) is produced by lymphocytes in areas of inflammation and connective tissue destruction. IFN inhibits collagen and DNA synthesis in cultured rat long bones and osteoblastic ROS 17/2.8 cells, suggesting that the periarticular loss of bone that occurs in inflammatory joint diseases may be due to IFN inhibition of bone formation. Since serum levels of bone gla protein (BGP) have been correlated with the bone formation rate, we studied the effect of IFN on production of this osteoblast-specific protein and steady state BGP messenger RNA (mRNA) levels in ROS 17/2.8 cells. RIA of BGP was done using an antibody raised against rat BGP peptide. BGP synthesis was stimulated with 10(-8) M 1,25-dihydroxyvitamin D3 24 h before and continuously after addition of recombinant rat IFN. IFN (100 U/ml) inhibited BGP secretion 52%, 78%, and 70% in the first, second, and third 24 h periods after IFN treatment, compared to control cells cultured with 1,25-dihydroxyvitamin D3 alone. The ED50 for IFN inhibition of BGP production was 3.3 U/ml (0.29 nM). Pulse labeling with [14C]leucine or [3H]proline during the last 4 h of culture revealed that IFN (3-100 U/ml) did not inhibit total protein secretion into the medium. The percent in...Continue Reading

Citations

Aug 1, 1993·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·N MayurM S Nanes
Oct 1, 1995·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·F J BuchinskyS Epstein
May 1, 1992·Journal of Cellular Biochemistry·J B Lian, G S Stein
Sep 1, 1995·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·M IshibeK Kaneda
Jan 1, 1991·Critical Reviews in Clinical Laboratory Sciences·M J Power, P F Fottrell
Feb 1, 1996·The American Journal of the Medical Sciences·J RubinM S Nanes
Jan 19, 2006·Journal of Cellular Physiology·Xian FanJanet Rubin
Jan 1, 1992·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·J B Lian, G S Stein

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