title: Differential effects of bisphenol A diglicydyl ether on bone quality and marrow adiposity in ovary-intact and ovariectomized rats.
abstract: Bisphenol A diglycidyl ether (BADGE), a PPARγ2 antagonist, has been shown to inhibit marrow adipogenesis and promote bone formation in intact animals. We investigated the impact of BADGE on a new and more clinically relevant physiological model, the ovariectomized (OVX) rat model. Forty female Wistar rats were divided into four treatment groups for 12 wk (n = 10/group): sham+vehicle, sham+BADGE, OVX+vehicle, and OVX+BADGE. Postmortem analyses included MRI, micro-CT, serological test, histomorphometry, biomechanical tests, RT-PCR, and Western blot. Overall, OVX induced a sequential marrow fat expansion accompanied by bone deterioration. Compared with OVX controls, BADGE reduced fat fraction of the distal femur by 36.3%, adipocyte density by 33.0%, adipocyte size by 28.6%, adipocyte volume percentage by 57.8%, and adipogenic markers PPARγ2 and C/EBPα by ∼50% in OVX rats. Similar results were observed in sham rats vs. vehicle. BADGE could promote bone quality in sham rats; however, BADGE did not significantly improve trabecular microarchitecture, biomechanical strength, and dynamic histomorphometric parameters except for trabecular separation in OVX rats. We concluded that early BADGE treatment at a dose of 30 mg/kg attenuates marrow adiposity in ovary-intact and OVX rats and stimulates bone formation in ovary-intact rats but does not significantly rescue bone quality in OVX rats.
authors.affiliation: Department of Radiology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; purenyi@163.com.
authors.forename: Guanwu
authors.initials: G
authors.lastname: Li
authors.affiliation: Xinzhuang Community Health Center, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Affiliated Hospital of North Sichuan Medical College, Sichuan, China.
authors.forename: Lingmi
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Radiology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gerontology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Spinal Disease Unit, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; and.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors.forename: Maki
authors.initials: M
authors.lastname: Polat
authors.affiliation: Department of Radiology, Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Shixin
authors.initials: S
authors.lastname: Chang
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000473:pathology; D050156:Adipogenesis / Q000187:drug effects; D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D002452:Cell Count; D048429:Cell Size; D050659:Core Binding Factor Alpha 1 Subunit / Q000187:drug effects / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology*; D005260:Female; D015675:Osteocalcin / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D055114:X-Ray Microtomography; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D022762:CCAAT-Enhancer-Binding Proteins; D002273:Carcinogens; D050659:Core Binding Factor Alpha 1 Subunit; D004852:Epoxy Compounds; D015675:Osteocalcin; D047495:PPAR gamma; C493717:Runx2 protein, rat; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds
keywords: PPARγ2 antagonist; marrow fat; osteoporosis; ovariectomy