title: Exposure to Excess Phenobarbital Negatively Influences the Osteogenesis of Chick Embryos.
abstract: Phenobarbital is an antiepileptic drug that is widely used to treat epilepsy in a clinical setting. However, a long term of phenobarbital administration in pregnant women may produce side effects on embryonic skeletogenesis. In this study, we aim to investigate the mechanism by which phenobarbital treatment induces developmental defects in long bones. We first determined that phenobarbital treatment decreased chondrogenesis and inhibited the proliferation of chondrocytes in chick embryos. Phenobarbital treatment also suppressed mineralization in bothin vivoandin vitrolong bone models. Next, we established that phenobarbital treatment delayed blood vessel invasion in a cartilage template, and this finding was supported by the down-regulation of vascular endothelial growth factor in the hypertrophic zone following phenobarbital treatment. Phenobarbital treatment inhibited tube formation and the migration of human umbilical vein endothelial cells. In addition, it impaired angiogenesis in chick yolk sac membrane model and chorioallantoic membrane model. In summary, phenobarbital exposure led to shortened lengths of long bones during embryogenesis, which might result from inhibiting mesenchyme differentiation, chondrocyte proliferation, and delaying mineralization by impairing vascular invasion.
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University Guangzhou, China.
authors.forename: Ren-Hao
authors.initials: RH
authors.lastname: Yang
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University Guangzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University Guangzhou, China.
authors.forename: Jian-Long
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University Guangzhou, China.
authors.forename: Zheng-Lai
authors.initials: ZL
authors.lastname: Ma
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University Guangzhou, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Division of Cell and Developmental Biology, University of Dundee Dundee, UK.
authors.forename: Manli
authors.initials: M
authors.lastname: Chuai
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University Guangzhou, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
keywords: angiogenesis; chick embryos; chondrogenesis; mineralization; osteogenesis; phenobarbital