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Open AccessArticle

Valproic Acid Impacts the Growth of Growth Plate Chondrocytes

1
Department of Pediatrics, Tungs’ Taichung Metroharbor Hospital, Taichung 435, Taiwan
2
Department of Medical research, Tungs’ Taichung Metroharbor Hospital, Taichung 435, Taiwan
3
Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 35053, Taiwan
4
Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan
5
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan
6
Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2020, 17(10), 3675; https://doi.org/10.3390/ijerph17103675
Received: 14 April 2020 / Revised: 13 May 2020 / Accepted: 21 May 2020 / Published: 22 May 2020
(This article belongs to the Special Issue Feature Papers in Children's Health)
A range of bone abnormalities including short stature have been reported to be associated with the use of antiepileptic drugs (AEDs) in children. Exactly how AEDs impact skeletal growth, however, is not clear. In the present study, rat growth plate chondrocytes were cultured to study the effects of AEDs, including valproic acid (VPA), oxcarbazepine (OXA), levetiracetam (LEV), lamotrigine (LTG), and topiramate (TPM) on the skeletal growth. VPA markedly reduced the number of chondrocytes by apoptosiswhile other AEDs had no effect. The apoptosis associated noncleaved and cleaved caspase 3, and caspases were increased by exposure to VPA, which up-regulated cyclooxygenase 2 (COX-2) mRNA and protein levels likely through histone acetylation. The COX-2 inhibitor NS-398 attenuated the effects of VPA up-regulating COX-2 expression and decreased VPA-induced caspase 3 expression. The use of VPA in children should be closely monitored or replaced, where appropriate, by AEDs which do not apparently affect the growth plate chondrocytes.
Keywords: growth plate chondrocyte; valproic acid; apoptosis; cyclooxygenase 2; histone acetylation growth plate chondrocyte; valproic acid; apoptosis; cyclooxygenase 2; histone acetylation
MDPI and ACS Style

Fan, H.-C.; Wang, S.-Y.; Peng, Y.-J.; Lee, H.-S. Valproic Acid Impacts the Growth of Growth Plate Chondrocytes. Int. J. Environ. Res. Public Health 2020, 17, 3675.

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