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...
Gespeichert in:
| Veröffentlicht in: | PloS one 2012-03, Vol.7 (3), p.e33168 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 3 |
| container_start_page | e33168 |
| container_title | PloS one |
| container_volume | 7 |
| creator | Zaman, Farasat Chrysis, Dionisios Huntjens, Kirsten Fadeel, Bengt Sävendahl, Lars |
| 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. |
| doi_str_mv | 10.1371/journal.pone.0033168 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1324435136</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A477065012</galeid><doaj_id>oai_doaj_org_article_e113584617d042c5868eee75db3e8f39</doaj_id><sourcerecordid>A477065012</sourcerecordid><originalsourceid>FETCH-LOGICAL-c795t-466b56f9fea5c1d7e6db7f1830cc66b48d466b1e24538cf94e6526a7fa01a2d63</originalsourceid><addsrcrecordid>eNqNk12L1DAUhoso7of-A9GCIHjRMWnapHMjjIsfAwsLft2GNDnpZGybmqTu7r83dbrLFBSkFz09ed6Xc056kuQZRitMGH6zt6PrRbsabA8rhAjBtHqQnOI1yTOaI_LwKD5JzrzfI1SSitLHyUmeF0VOWXWa7Dd1K4KxfWp1GnaQDs5mYrBDsMHI6SuA6dN34uYQy-DTzkhItbNd2rSjtNK6iFqjMtOrUYJK61hS2jh7HXap6QZhXAd9eJI80qL18HR-nyffPrz_evEpu7z6uL3YXGaSrcuQFZTWJdVrDaKUWDGgqmYaVwRJGY-KSk0EhryI3Ui9LoCWORVMC4RFrig5T14cfIfWej6PyXNMYtOkxGQitgdCWbHngzOdcLfcCsP_JKxruJh6aoEDxqSsCoqZQkUuy4pWAMBKVROoNFlHr-zg5a9hGOuF25z6ESPgsdqcoMi_nasb6w6UjINxol3Ilie92fHG_uKEIMYIjgYvZwNnf47gwz9anKlGxC5Mr200k53xkm8KxhAtEc4jtfoLFR8F8ZLjLWoT8wvB64UgMgFuQiNG7_n2y-f_Z6--L9lXR-wORBt23rbj9Gf6JVgcQOms9w70_eQw4tNe3E2DT3vB572IsufHU78X3S0C-Q0i1Anf</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1324435136</pqid></control><display><type>article</type><title>Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>SWEPUB Freely available online</source><source>Free Full-Text Journals in Chemistry</source><creator>Zaman, Farasat ; Chrysis, Dionisios ; Huntjens, Kirsten ; Fadeel, Bengt ; Sävendahl, Lars</creator><creatorcontrib>Zaman, Farasat ; Chrysis, Dionisios ; Huntjens, Kirsten ; Fadeel, Bengt ; Sävendahl, Lars</creatorcontrib><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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0033168</identifier><identifier>PMID: 22442678</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Ablation ; Adolescent ; Animals ; Apoptosis ; Apoptosis - drug effects ; BAX protein ; Bcl-2 protein ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Biocompatibility ; Biology ; Biomedical materials ; Bone growth ; Bones ; Cancer therapies ; Cartilage ; Cell growth ; Cell Line ; Children ; Children & youth ; Childrens health ; Chondrocytes ; Chondrocytes - metabolism ; Chondrocytes - pathology ; Chrysis ; Dexamethasone ; Dexamethasone - adverse effects ; Dexamethasone - pharmacology ; Dual energy X-ray absorptiometry ; Endocrinology ; Female ; Females ; Gene expression ; Glucocorticoids ; Glucocorticoids - adverse effects ; Glucocorticoids - pharmacology ; Growth ; Growth plate ; Growth Plate - metabolism ; Growth Plate - pathology ; Humans ; Impairment ; Inflammatory diseases ; Leukemia ; Lindgren, Astrid (1907-2002) ; Male ; Males ; Medicine ; Mice ; Mice, Mutant Strains ; Mitochondria ; Obesity - chemically induced ; Obesity - genetics ; Obesity - metabolism ; Osteoporosis ; Osteoporosis - chemically induced ; Osteoporosis - genetics ; Osteoporosis - metabolism ; Pediatrics ; Peptides ; Phosphorylation ; Proteins ; Ribonucleic acid ; RNA ; Rodents ; siRNA ; Somatotropin ; Steroids (Organic compounds) ; Women</subject><ispartof>PloS one, 2012-03, Vol.7 (3), p.e33168</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Zaman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Zaman et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c795t-466b56f9fea5c1d7e6db7f1830cc66b48d466b1e24538cf94e6526a7fa01a2d63</citedby><cites>FETCH-LOGICAL-c795t-466b56f9fea5c1d7e6db7f1830cc66b48d466b1e24538cf94e6526a7fa01a2d63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307731/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307731/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22442678$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:124626269$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Zaman, Farasat</creatorcontrib><creatorcontrib>Chrysis, Dionisios</creatorcontrib><creatorcontrib>Huntjens, Kirsten</creatorcontrib><creatorcontrib>Fadeel, Bengt</creatorcontrib><creatorcontrib>Sävendahl, Lars</creatorcontrib><title>Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Ablation</subject><subject>Adolescent</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>BAX protein</subject><subject>Bcl-2 protein</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Biocompatibility</subject><subject>Biology</subject><subject>Biomedical materials</subject><subject>Bone growth</subject><subject>Bones</subject><subject>Cancer therapies</subject><subject>Cartilage</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Children</subject><subject>Children & youth</subject><subject>Childrens health</subject><subject>Chondrocytes</subject><subject>Chondrocytes - metabolism</subject><subject>Chondrocytes - pathology</subject><subject>Chrysis</subject><subject>Dexamethasone</subject><subject>Dexamethasone - adverse effects</subject><subject>Dexamethasone - pharmacology</subject><subject>Dual energy X-ray absorptiometry</subject><subject>Endocrinology</subject><subject>Female</subject><subject>Females</subject><subject>Gene expression</subject><subject>Glucocorticoids</subject><subject>Glucocorticoids - adverse effects</subject><subject>Glucocorticoids - pharmacology</subject><subject>Growth</subject><subject>Growth plate</subject><subject>Growth Plate - metabolism</subject><subject>Growth Plate - pathology</subject><subject>Humans</subject><subject>Impairment</subject><subject>Inflammatory diseases</subject><subject>Leukemia</subject><subject>Lindgren, Astrid (1907-2002)</subject><subject>Male</subject><subject>Males</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Mitochondria</subject><subject>Obesity - chemically induced</subject><subject>Obesity - genetics</subject><subject>Obesity - metabolism</subject><subject>Osteoporosis</subject><subject>Osteoporosis - chemically induced</subject><subject>Osteoporosis - genetics</subject><subject>Osteoporosis - metabolism</subject><subject>Pediatrics</subject><subject>Peptides</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Rodents</subject><subject>siRNA</subject><subject>Somatotropin</subject><subject>Steroids (Organic compounds)</subject><subject>Women</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>D8T</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7of-A9GCIHjRMWnapHMjjIsfAwsLft2GNDnpZGybmqTu7r83dbrLFBSkFz09ed6Xc056kuQZRitMGH6zt6PrRbsabA8rhAjBtHqQnOI1yTOaI_LwKD5JzrzfI1SSitLHyUmeF0VOWXWa7Dd1K4KxfWp1GnaQDs5mYrBDsMHI6SuA6dN34uYQy-DTzkhItbNd2rSjtNK6iFqjMtOrUYJK61hS2jh7HXap6QZhXAd9eJI80qL18HR-nyffPrz_evEpu7z6uL3YXGaSrcuQFZTWJdVrDaKUWDGgqmYaVwRJGY-KSk0EhryI3Ui9LoCWORVMC4RFrig5T14cfIfWej6PyXNMYtOkxGQitgdCWbHngzOdcLfcCsP_JKxruJh6aoEDxqSsCoqZQkUuy4pWAMBKVROoNFlHr-zg5a9hGOuF25z6ESPgsdqcoMi_nasb6w6UjINxol3Ilie92fHG_uKEIMYIjgYvZwNnf47gwz9anKlGxC5Mr200k53xkm8KxhAtEc4jtfoLFR8F8ZLjLWoT8wvB64UgMgFuQiNG7_n2y-f_Z6--L9lXR-wORBt23rbj9Gf6JVgcQOms9w70_eQw4tNe3E2DT3vB572IsufHU78X3S0C-Q0i1Anf</recordid><startdate>20120319</startdate><enddate>20120319</enddate><creator>Zaman, Farasat</creator><creator>Chrysis, Dionisios</creator><creator>Huntjens, Kirsten</creator><creator>Fadeel, Bengt</creator><creator>Sävendahl, Lars</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><scope>DOA</scope></search><sort><creationdate>20120319</creationdate><title>Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment</title><author>Zaman, Farasat ; Chrysis, Dionisios ; Huntjens, Kirsten ; Fadeel, Bengt ; Sävendahl, Lars</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c795t-466b56f9fea5c1d7e6db7f1830cc66b48d466b1e24538cf94e6526a7fa01a2d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Ablation</topic><topic>Adolescent</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>BAX protein</topic><topic>Bcl-2 protein</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Biocompatibility</topic><topic>Biology</topic><topic>Biomedical materials</topic><topic>Bone growth</topic><topic>Bones</topic><topic>Cancer therapies</topic><topic>Cartilage</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Children</topic><topic>Children & youth</topic><topic>Childrens health</topic><topic>Chondrocytes</topic><topic>Chondrocytes - metabolism</topic><topic>Chondrocytes - pathology</topic><topic>Chrysis</topic><topic>Dexamethasone</topic><topic>Dexamethasone - adverse effects</topic><topic>Dexamethasone - pharmacology</topic><topic>Dual energy X-ray absorptiometry</topic><topic>Endocrinology</topic><topic>Female</topic><topic>Females</topic><topic>Gene expression</topic><topic>Glucocorticoids</topic><topic>Glucocorticoids - adverse effects</topic><topic>Glucocorticoids - pharmacology</topic><topic>Growth</topic><topic>Growth plate</topic><topic>Growth Plate - metabolism</topic><topic>Growth Plate - pathology</topic><topic>Humans</topic><topic>Impairment</topic><topic>Inflammatory diseases</topic><topic>Leukemia</topic><topic>Lindgren, Astrid (1907-2002)</topic><topic>Male</topic><topic>Males</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>Mitochondria</topic><topic>Obesity - chemically induced</topic><topic>Obesity - genetics</topic><topic>Obesity - metabolism</topic><topic>Osteoporosis</topic><topic>Osteoporosis - chemically induced</topic><topic>Osteoporosis - genetics</topic><topic>Osteoporosis - metabolism</topic><topic>Pediatrics</topic><topic>Peptides</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Rodents</topic><topic>siRNA</topic><topic>Somatotropin</topic><topic>Steroids (Organic compounds)</topic><topic>Women</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zaman, Farasat</creatorcontrib><creatorcontrib>Chrysis, Dionisios</creatorcontrib><creatorcontrib>Huntjens, Kirsten</creatorcontrib><creatorcontrib>Fadeel, Bengt</creatorcontrib><creatorcontrib>Sävendahl, Lars</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zaman, Farasat</au><au>Chrysis, Dionisios</au><au>Huntjens, Kirsten</au><au>Fadeel, Bengt</au><au>Sävendahl, Lars</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-03-19</date><risdate>2012</risdate><volume>7</volume><issue>3</issue><spage>e33168</spage><pages>e33168-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22442678</pmid><doi>10.1371/journal.pone.0033168</doi><tpages>e33168</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-03, Vol.7 (3), p.e33168 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1324435136 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SWEPUB Freely available online; Free Full-Text Journals in Chemistry |
| subjects | Ablation Adolescent Animals Apoptosis Apoptosis - drug effects BAX protein Bcl-2 protein bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Biocompatibility Biology Biomedical materials Bone growth Bones Cancer therapies Cartilage Cell growth Cell Line Children Children & youth Childrens health Chondrocytes Chondrocytes - metabolism Chondrocytes - pathology Chrysis Dexamethasone Dexamethasone - adverse effects Dexamethasone - pharmacology Dual energy X-ray absorptiometry Endocrinology Female Females Gene expression Glucocorticoids Glucocorticoids - adverse effects Glucocorticoids - pharmacology Growth Growth plate Growth Plate - metabolism Growth Plate - pathology Humans Impairment Inflammatory diseases Leukemia Lindgren, Astrid (1907-2002) Male Males Medicine Mice Mice, Mutant Strains Mitochondria Obesity - chemically induced Obesity - genetics Obesity - metabolism Osteoporosis Osteoporosis - chemically induced Osteoporosis - genetics Osteoporosis - metabolism Pediatrics Peptides Phosphorylation Proteins Ribonucleic acid RNA Rodents siRNA Somatotropin Steroids (Organic compounds) Women |
| title | Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T00%3A35%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ablation%20of%20the%20pro-apoptotic%20protein%20Bax%20protects%20mice%20from%20glucocorticoid-induced%20bone%20growth%20impairment&rft.jtitle=PloS%20one&rft.au=Zaman,%20Farasat&rft.date=2012-03-19&rft.volume=7&rft.issue=3&rft.spage=e33168&rft.pages=e33168-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0033168&rft_dat=%3Cgale_plos_%3EA477065012%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1324435136&rft_id=info:pmid/22442678&rft_galeid=A477065012&rft_doaj_id=oai_doaj_org_article_e113584617d042c5868eee75db3e8f39&rfr_iscdi=true |