The influence of auranofin, a clinically established antiarthritic gold drug, on bone metabolism: analysis of its effects on human multipotent adipose-derived stem cells, taken as a model.
Auranofin is a gold-based antiarthritic drug in clinical use for more that 25 years. However, in spite of a long established use, its specific effects on bone metabolism are still greatly controversial. We have analyzed in vitro the actions of auranofin on human multipotent adipose-derived stem (hMADS) cells, used as a model for bone metabolism, since these cells were reported to undergo osteogenesis both in vitro and in vivo. Cytotoxicity of auranofin on hMADS cells, differentiated into osteoblasts, was initially assessed. Thereafter, the consequences of exposure to nontoxic but clinically relevant auranofin concentrations were analyzed by monitoring the seleno-protein glutathione peroxidase 3 or alkaline phosphatase, a characteristic biomarker of osteogenesis. Notably, we found that chronic treatment with auranofin alters only weakly the levels of alkaline phosphatase, thus implying an overall modest effect on osteogenesis. In contrast, auranofin turned out to greatly affect glutathione peroxidase 3 activity. The possible medical implications of these findings are discussed.
Chiellini
Chiara
C
ISBDC, Université de Nice Sophia-Antipolis, CNRS, 28 avenue de Valrose, F-06100 Nice, (phone: +33 492 07 64 29; fax: +33 492 07 64 04).
Casini
Angela
A
Department of Chemistry, University of Florence, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Florence (phone: +39 055 4573388; fax: +39 055 45 73 385).
Cochet
Olivia
O
ISBDC, Université de Nice Sophia-Antipolis, CNRS, 28 avenue de Valrose, F-06100 Nice, (phone: +33 492 07 64 29; fax: +33 492 07 64 04).
Gabbiani
Chiara
C
Department of Chemistry, University of Florence, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Florence (phone: +39 055 4573388; fax: +39 055 45 73 385).
Ailhaud
Gérard
G
ISBDC, Université de Nice Sophia-Antipolis, CNRS, 28 avenue de Valrose, F-06100 Nice, (phone: +33 492 07 64 29; fax: +33 492 07 64 04).
Dani
Christian
C
ISBDC, Université de Nice Sophia-Antipolis, CNRS, 28 avenue de Valrose, F-06100 Nice, (phone: +33 492 07 64 29; fax: +33 492 07 64 04).
Messori
Luigi
L
Department of Chemistry, University of Florence, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Florence (phone: +39 055 4573388; fax: +39 055 45 73 385).
Amri
Ez-Zoubir
EZ
ISBDC, Université de Nice Sophia-Antipolis, CNRS, 28 avenue de Valrose, F-06100 Nice, (phone: +33 492 07 64 29; fax: +33 492 07 64 04).
D000273:Adipose Tissue / Q000166:cytology*; D001168:Arthritis / Q000188:drug therapy*; D001310:Auranofin / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008954:Models, Biological; D010012:Osteogenesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*
D012333:RNA, Messenger; D001310:Auranofin; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase