Effect of auranofin on resorption, prostaglandin synthesis and ultrastructure of bone cells in cultured mouse calvaria.
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.
Ludwig Boltzmann Research Unit for Clinical and Experimental Osteology, University of Vienna Medical School, Austria.
K
K
Klaushofer
O
O
Hoffmann
H
H
Hörandner
S
S
Karasegh
N
N
Fratzl-Zelman
H J
HJ
Leis
H
H
Gleispach
K
K
Koller
M
M
Peterlik
D000818:Animals; D001310:Auranofin / Q000494:pharmacology* / Q000633:toxicity; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000648:ultrastructure; D002478:Cells, Cultured; D051379:Mice; D011453:Prostaglandins / Q000096:biosynthesis*; D012886:Skull
D011453:Prostaglandins; D001310:Auranofin