Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment.
Dexamethasone (Dexa) is a widely used glucocorticoid to treat inflammatory diseases; however, a multitude of undesired effects have been reported to arise from this treatment including osteoporosis, obesity, and in children decreased longitudinal bone growth. We and others have previously shown that...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3307731?pdf=render |
| _version_ | 1818258385340989440 |
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| author | Farasat Zaman Dionisios Chrysis Kirsten Huntjens Bengt Fadeel Lars Sävendahl |
| author_facet | Farasat Zaman Dionisios Chrysis Kirsten Huntjens Bengt Fadeel Lars Sävendahl |
| author_sort | Farasat Zaman |
| collection | DOAJ |
| description | Dexamethasone (Dexa) is a widely used glucocorticoid to treat inflammatory diseases; however, a multitude of undesired effects have been reported to arise from this treatment including osteoporosis, obesity, and in children decreased longitudinal bone growth. We and others have previously shown that glucocorticoids induce apoptosis in growth plate chondrocytes. Here, we hypothesized that Bax, a pro-apoptotic member of the Bcl-2 family, plays a key role in Dexa-induced chondrocyte apoptosis and bone growth impairment. Indeed, experiments in the human HCS-2/8 chondrocytic cell line demonstrated that silencing of Bax expression using small-interfering (si) RNA efficiently blocked Dexa-induced apoptosis. Furthermore, ablation of Bax in female mice protected against Dexa-induced bone growth impairment. Finally, Bax activation by Dexa was confirmed in human growth plate cartilage specimens cultured ex vivo. Our findings could therefore open the door for new therapeutic approaches to prevent glucocorticoid-induced bone growth impairment through specific targeting of Bax. |
| first_indexed | 2024-12-12T17:58:42Z |
| format | Article |
| id | doaj.art-e113584617d042c5868eee75db3e8f39 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T17:58:42Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e113584617d042c5868eee75db3e8f392022-12-22T00:16:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3316810.1371/journal.pone.0033168Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment.Farasat ZamanDionisios ChrysisKirsten HuntjensBengt FadeelLars SävendahlDexamethasone (Dexa) is a widely used glucocorticoid to treat inflammatory diseases; however, a multitude of undesired effects have been reported to arise from this treatment including osteoporosis, obesity, and in children decreased longitudinal bone growth. We and others have previously shown that glucocorticoids induce apoptosis in growth plate chondrocytes. Here, we hypothesized that Bax, a pro-apoptotic member of the Bcl-2 family, plays a key role in Dexa-induced chondrocyte apoptosis and bone growth impairment. Indeed, experiments in the human HCS-2/8 chondrocytic cell line demonstrated that silencing of Bax expression using small-interfering (si) RNA efficiently blocked Dexa-induced apoptosis. Furthermore, ablation of Bax in female mice protected against Dexa-induced bone growth impairment. Finally, Bax activation by Dexa was confirmed in human growth plate cartilage specimens cultured ex vivo. Our findings could therefore open the door for new therapeutic approaches to prevent glucocorticoid-induced bone growth impairment through specific targeting of Bax.http://europepmc.org/articles/PMC3307731?pdf=render |
| spellingShingle | Farasat Zaman Dionisios Chrysis Kirsten Huntjens Bengt Fadeel Lars Sävendahl Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment. PLoS ONE |
| title | Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment. |
| title_full | Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment. |
| title_fullStr | Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment. |
| title_full_unstemmed | Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment. |
| title_short | Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment. |
| title_sort | ablation of the pro apoptotic protein bax protects mice from glucocorticoid induced bone growth impairment |
| url | http://europepmc.org/articles/PMC3307731?pdf=render |
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