title: Thiazolidinediones (TZDs) affect osteoblast viability and biomarkers independently of the TZD effects on aromatase.
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.
authors.affiliation: Division of Endocrinology, Department of Medicine, The Friedman Diabetes Institute, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, New York 10003, USA.
authors.forename: A
authors.initials: A
authors.lastname: Seth
authors.forename: V
authors.initials: V
authors.lastname: Sy
authors.forename: A
authors.initials: A
authors.lastname: Pareek
authors.forename: P
authors.initials: P
authors.lastname: Suwandhi
authors.forename: Z
authors.initials: Z
authors.lastname: Rosenwaks
authors.forename: L
authors.initials: L
authors.lastname: Poretsky
authors.forename: D
authors.initials: D
authors.lastname: Seto-Young
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001391:Azo Compounds / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006416:Hematoxylin / Q000378:metabolism; D006801:Humans; D051379:Mice; D019301:Oleic Acid / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D015675:Osteocalcin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D001391:Azo Compounds; D015415:Biomarkers; D024042:Collagen Type I; D012333:RNA, Messenger; D045162:Thiazolidinediones; D015675:Osteocalcin; D019301:Oleic Acid; D004958:Estradiol; D001141:Aromatase; D000469:Alkaline Phosphatase; C011049:oil red O; D006416:Hematoxylin