Valproic Acid Impacts the Growth of Growth Plate Chondrocytes
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...
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| Veröffentlicht in: | International journal of environmental research and public health 2020-05, Vol.17 (10), p.3675 |
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| description | 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. |
| doi_str_mv | 10.3390/ijerph17103675 |
| format | Article |
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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.</description><identifier>ISSN: 1660-4601</identifier><identifier>ISSN: 1661-7827</identifier><identifier>EISSN: 1660-4601</identifier><identifier>DOI: 10.3390/ijerph17103675</identifier><identifier>PMID: 32456093</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Abnormalities ; Acetylation ; Animals ; Anticonvulsants - toxicity ; Antiepileptic agents ; Apoptosis ; Cartilage ; Caspase-3 ; Cell culture ; Cells, Cultured ; Child ; Children ; Chondrocytes ; Chondrocytes - drug effects ; Convulsions & seizures ; COX-2 inhibitors ; Cyclooxygenase-2 ; Epilepsy ; Etiracetam ; Gene expression ; Growth plate ; Growth Plate - drug effects ; Humans ; Lamotrigine ; Medical research ; Metabolism ; Metabolites ; mRNA ; Oxcarbazepine ; Polyclonal antibodies ; Proteins ; Rats ; Topiramate ; Valproic acid ; Valproic Acid - toxicity</subject><ispartof>International journal of environmental research and public health, 2020-05, Vol.17 (10), p.3675</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-67094176eab596a1a287a80c3af207b86c77212161831e12cf1e3ea212f696cb3</citedby><cites>FETCH-LOGICAL-c418t-67094176eab596a1a287a80c3af207b86c77212161831e12cf1e3ea212f696cb3</cites><orcidid>0000-0003-4630-2103</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277424/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277424/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32456093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fan, Hueng-Chuen</creatorcontrib><creatorcontrib>Wang, Shih-Yu</creatorcontrib><creatorcontrib>Peng, Yi-Jen</creatorcontrib><creatorcontrib>Lee, Herng-Sheng</creatorcontrib><title>Valproic Acid Impacts the Growth of Growth Plate Chondrocytes</title><title>International journal of environmental research and public health</title><addtitle>Int J Environ Res Public Health</addtitle><description>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.</description><subject>Abnormalities</subject><subject>Acetylation</subject><subject>Animals</subject><subject>Anticonvulsants - toxicity</subject><subject>Antiepileptic agents</subject><subject>Apoptosis</subject><subject>Cartilage</subject><subject>Caspase-3</subject><subject>Cell culture</subject><subject>Cells, Cultured</subject><subject>Child</subject><subject>Children</subject><subject>Chondrocytes</subject><subject>Chondrocytes - drug effects</subject><subject>Convulsions & seizures</subject><subject>COX-2 inhibitors</subject><subject>Cyclooxygenase-2</subject><subject>Epilepsy</subject><subject>Etiracetam</subject><subject>Gene expression</subject><subject>Growth plate</subject><subject>Growth Plate - drug effects</subject><subject>Humans</subject><subject>Lamotrigine</subject><subject>Medical research</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>mRNA</subject><subject>Oxcarbazepine</subject><subject>Polyclonal antibodies</subject><subject>Proteins</subject><subject>Rats</subject><subject>Topiramate</subject><subject>Valproic acid</subject><subject>Valproic Acid - toxicity</subject><issn>1660-4601</issn><issn>1661-7827</issn><issn>1660-4601</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpVUMFKAzEUDKLYWr16lAXPW_OSbLI5KJSitVDQg3oN2TTrbtk2a5Iq_XtXWkt7esN782aGQega8JBSie_qhfVtBQIw5SI7QX3gHKeMYzg9wD10EcICY5ozLs9RjxKWcSxpH91_6Kb1rjbJyNTzZLpstYkhiZVNJt79xCpx5T96bXS0ybhyq7l3ZhNtuERnpW6CvdrNAXp_enwbP6ezl8l0PJqlhkEeUy6wZCC41UUmuQZNcqFzbKguCRZFzo0QBAhwyClYIKYES63uViWX3BR0gB62uu26WNq5savodaNaXy-13yina3V8WdWV-nTfShAhGGGdwO1OwLuvtQ1RLdzar7rMijDMZS4yKTrWcMsy3oXgbbl3AKz-6lbHdXcPN4e59vT_fukvN7x7pA</recordid><startdate>20200522</startdate><enddate>20200522</enddate><creator>Fan, Hueng-Chuen</creator><creator>Wang, Shih-Yu</creator><creator>Peng, Yi-Jen</creator><creator>Lee, Herng-Sheng</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4630-2103</orcidid></search><sort><creationdate>20200522</creationdate><title>Valproic Acid Impacts the Growth of Growth Plate Chondrocytes</title><author>Fan, Hueng-Chuen ; 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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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32456093</pmid><doi>10.3390/ijerph17103675</doi><orcidid>https://orcid.org/0000-0003-4630-2103</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Abnormalities Acetylation Animals Anticonvulsants - toxicity Antiepileptic agents Apoptosis Cartilage Caspase-3 Cell culture Cells, Cultured Child Children Chondrocytes Chondrocytes - drug effects Convulsions & seizures COX-2 inhibitors Cyclooxygenase-2 Epilepsy Etiracetam Gene expression Growth plate Growth Plate - drug effects Humans Lamotrigine Medical research Metabolism Metabolites mRNA Oxcarbazepine Polyclonal antibodies Proteins Rats Topiramate Valproic acid Valproic Acid - toxicity |
| title | Valproic Acid Impacts the Growth of Growth Plate Chondrocytes |
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