Exposure to excess phenobarbital negatively influences the osteogenesis of chick embryos
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 t...
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| Format: | Article |
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Frontiers Media S.A.
2016-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00349/full |
| _version_ | 1818306990950055936 |
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| author | Yu Yan Xin Cheng Ren-hao Yang He Li Jian-long Chen Zheng-lai Ma Guang Wang Manli Chuai Xuesong Yang |
| author_facet | Yu Yan Xin Cheng Ren-hao Yang He Li Jian-long Chen Zheng-lai Ma Guang Wang Manli Chuai Xuesong Yang |
| author_sort | Yu Yan |
| collection | DOAJ |
| description | 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 both in vivo and in vitro long 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. |
| first_indexed | 2024-12-13T06:51:16Z |
| format | Article |
| id | doaj.art-58d7283a1ed2409ba89fc762be49dcc1 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T06:51:16Z |
| publishDate | 2016-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-58d7283a1ed2409ba89fc762be49dcc12022-12-21T23:56:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122016-09-01710.3389/fphar.2016.00349217641Exposure to excess phenobarbital negatively influences the osteogenesis of chick embryosYu Yan0Xin Cheng1Ren-hao Yang2He Li3Jian-long Chen4Zheng-lai Ma5Guang Wang6Manli Chuai7Xuesong Yang8Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan UniversityDivision of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan UniversityDivision of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan UniversityDivision of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan UniversityDivision of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan UniversityDivision of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan UniversityDivision of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan UniversityDivision of Cell and Developmental Biology, University of DundeeDivision of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan UniversityPhenobarbital 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 both in vivo and in vitro long 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.http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00349/fullChondrogenesisOsteogenesisPhenobarbitalAngiogenesismineralizationChick embryos |
| spellingShingle | Yu Yan Xin Cheng Ren-hao Yang He Li Jian-long Chen Zheng-lai Ma Guang Wang Manli Chuai Xuesong Yang Exposure to excess phenobarbital negatively influences the osteogenesis of chick embryos Frontiers in Pharmacology Chondrogenesis Osteogenesis Phenobarbital Angiogenesis mineralization Chick embryos |
| title | Exposure to excess phenobarbital negatively influences the osteogenesis of chick embryos |
| title_full | Exposure to excess phenobarbital negatively influences the osteogenesis of chick embryos |
| title_fullStr | Exposure to excess phenobarbital negatively influences the osteogenesis of chick embryos |
| title_full_unstemmed | Exposure to excess phenobarbital negatively influences the osteogenesis of chick embryos |
| title_short | Exposure to excess phenobarbital negatively influences the osteogenesis of chick embryos |
| title_sort | exposure to excess phenobarbital negatively influences the osteogenesis of chick embryos |
| topic | Chondrogenesis Osteogenesis Phenobarbital Angiogenesis mineralization Chick embryos |
| url | http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00349/full |
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