Thiazolidinediones (TZDs) affect osteoblast viability and biomarkers independently of the TZD effects on aromatase.
Horm Metab Res
; 45(1): 1-8, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-22878908
ABSTRACT
Thiazolidinediones (TZDs) are insulin sensitizers used for treatment of diabetes. We have previously reported that TZDs reduce estrogen synthesis by inhibiting aromatase activity in human granulosa cells (HGC). Multiple clinical trials demonstrated that TZDs increase the risk of fractures in postmenopausal women with type 2 diabetes. We studied mouse osteoblasts alone or in a co-culture with HGC to determine whether TZD inhibition of aromatase plays a role in their effects on bone metabolism. Mouse osteoblasts were cultured with and without HGC, and incubated in a medium with or without testosterone, pioglitazone or rosiglitazone. Cell growth, oleic acid uptake, alkaline phosphatase activity, and osteocalcin production were measured. TZDs inhibited estradiol production by up to 84% in HGC/mouse osteoblast co-cultures. TZDs induced mouse osteoblast death and increased oleic acid uptake. TZDs also inhibited alkaline phosphatase activity (58-75%, p<0.046) and osteocalcin production (52-75%, p<0.031). For all the parameters, there were no significant differences between the osteoblast cultures alone and the HCG/osteoblast co-cultures. TZD effects on osteoblast viability, oleic acid uptake, alkaline phosphatase and osteocalcin production are independent of their effects on aromatase.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Aromatase
/
Tiazolidinedionas
Limite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Horm Metab Res
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos