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Effect of auranofin on resorption, prostaglandin synthesis and ultrastructure of bone cells in cultured mouse calvaria.

Authors :
Klaushofer K
Hoffmann O
Hörandner H
Karasegh S
Fratzl-Zelman N
Leis HJ
Gleispach H
Koller K
Peterlik M
Source :
The Journal of rheumatology [J Rheumatol] 1989 Jun; Vol. 16 (6), pp. 749-56.
Publication Year :
1989

Abstract

Auranofin (AF) in concentrations between 3 x 10(-7) and 3 x 10(-6) mol/l stimulated bone resorption in cultured neonatal mouse calvariae significantly with 1 x 10(-6) mol/l being most potent. Complete inhibition by 5 x 10(-7) mol/l indomethacin and increased medium concentrations of prostaglandin (PG) E2 and 6-keto-PGF1 alpha after 72 h indicate a PG mediated mechanism. Morphology revealed active osteoclasts. Cytotoxic effects were observed with 3 x 10(-6) and 1 x 10(-5) mol/l AF with osteocytes and osteoblasts being considerably more sensitive than osteoclasts. The latter concentrations inhibited bone resorption stimulated by parathyroid hormone (PTH) 1,25-dihydroxyvitamin D3, PGE2, thrombin and interleukin 1. The stimulatory effect of AF on PG production and subsequent bone resorption could limit its therapeutic usefulness.

Details

Language :
English
ISSN :
0315-162X
Volume :
16
Issue :
6
Database :
MEDLINE
Journal :
The Journal of rheumatology
Publication Type :
Academic Journal
Accession number :
2778756