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.
Klaushofer
K
K
Ludwig Boltzmann Research Unit for Clinical and Experimental Osteology, University of Vienna Medical School, Austria.
Hoffmann
O
O
Hörandner
H
H
Karasegh
S
S
Fratzl-Zelman
N
N
Leis
H J
HJ
Gleispach
H
H
Koller
K
K
Peterlik
M
M
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