Thiazolidinediones (TZDs) Affect Osteoblast Viability and Biomarkers Independently of the TZD Effects on Aromatase

A. Seth, V. Sy, A. Pareek, P. Suwandhi, Z. Rosenwaks, L. Poretsky, D. Seto-Young

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalHormone and Metabolic Research
Volume45
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • bone homeostasis
  • oral antidiabetic drugs
  • osteoblast

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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