title: Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts.
abstract: OBJECTIVE
  Bisphenol A (BPA), a major component of epoxy resins used in protective coatings, is a known endocrine-disrupting chemical. BPA has the ability of binding to estrogen receptors. In the current paper, we examine the direct effects of bisphenol A on in vitro osteoclast and osteoblast culture systems.
  
  
  METHODS
  We evaluated the effects of BPA on osteoclast formation using bone marrow-derived macrophages and RAW 264.7 cells and on osteoblast differentiation using MC3T3-E1 cells.
  
  
  RESULTS
  BPA significantly inhibited RANKL-induced, TRAP-positive multinucleated cell formation in bone marrow-derived macrophages and RAW 264.7 cell cultures in a dose-dependent manner (0.5 μM to 12.5 μM). We observed suppression of ERK, JNK, AKT, and p38 mitogen-activated protein kinases induced by RANKL in Western blotting after BPA treatment in RAW 264.7 cells. Furthermore, BPA suppressed Bcl-2 (anti-apoptotic) while stimulating Bax (pro-apoptotic) protein expression in RAW 264.7 cells. Bisphenol A also significantly suppressed ALP activities and bone nodule formation in MC3T3-E1 cell cultures. Specifically, the expression of Bcl-2 protein was decreased, and changes in expression of caspases 3, 8, and 9 were detected by BPA treatment in both cells.
  
  
  CONCLUSIONS
  We found that bisphenol A directly suppressed both osteoclastic and osteoblastic activities in vitro. Our data suggest that bisphenol A suppresses cell differentiation and survival.
authors.affiliation: Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Gangdong-gu, Seoul 134-727, Republic of Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Hwang
authors.forename: Kwan Hee
authors.initials: KH
authors.lastname: Min
authors.forename: Kyoung Hee
authors.initials: KH
authors.lastname: Choi
authors.forename: You Cheol
authors.initials: YC
authors.lastname: Hwang
authors.forename: In-Kyung
authors.initials: IK
authors.lastname: Jeong
authors.forename: Kyu Jeung
authors.initials: KJ
authors.lastname: Ahn
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Chung
authors.forename: Jae Suk
authors.initials: JS
authors.lastname: Chang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D053245:RANK Ligand / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; D053245:RANK Ligand; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Apoptosis; Bisphenol A; Differentiation; Osteoblasts; Osteoclasts