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In vivo effects of zoledronic acid on oral mucosal epithelial cells
Oral Diseases (2011) 17, 291–297 Objective: Osteonecrosis of the jaw is a serious complication of bisphosphonate treatment for which the pathophysiology is unknown. The purpose of this study was to investigate whether in vivo zoledronic acid (ZA) induces alterations in cell proliferation, apoptosis...
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| Published in: | Oral diseases 2011-04, Vol.17 (3), p.291-297 |
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| container_end_page | 297 |
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| container_start_page | 291 |
| container_title | Oral diseases |
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| creator | Allam, E Allen, MR Chu, T-M Ghoneima, A Jack Windsor, L |
| description | Oral Diseases (2011) 17, 291–297
Objective: Osteonecrosis of the jaw is a serious complication of bisphosphonate treatment for which the pathophysiology is unknown. The purpose of this study was to investigate whether in vivo zoledronic acid (ZA) induces alterations in cell proliferation, apoptosis, and matrix metalloproteinases (MMPs) expression in oral mucosal epithelial cells.
Methods: One‐year‐old dogs were either untreated (control group) or given high doses of intravenous ZA (ZA group) for 3 months. The doses of ZA were equivalent to those given to cancer patients, yet were administered two times more frequently (every 2 weeks). Mucosal tissues were assessed immunohistochemically for cell proliferation (proliferating cell nuclear antigen, PCNA), matrix metalloproteinase (MMP) expression, and apoptosis (caspase 3 and TUNEL).
Results: There were no significant differences between the groups with respect to PCNA, MMP‐2, MMP‐14, and TUNEL positive cells. However, the expression of MMP‐9 was significantly higher in the control group than in the ZA group (P |
| doi_str_mv | 10.1111/j.1601-0825.2010.01739.x |
| format | article |
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Objective: Osteonecrosis of the jaw is a serious complication of bisphosphonate treatment for which the pathophysiology is unknown. The purpose of this study was to investigate whether in vivo zoledronic acid (ZA) induces alterations in cell proliferation, apoptosis, and matrix metalloproteinases (MMPs) expression in oral mucosal epithelial cells.
Methods: One‐year‐old dogs were either untreated (control group) or given high doses of intravenous ZA (ZA group) for 3 months. The doses of ZA were equivalent to those given to cancer patients, yet were administered two times more frequently (every 2 weeks). Mucosal tissues were assessed immunohistochemically for cell proliferation (proliferating cell nuclear antigen, PCNA), matrix metalloproteinase (MMP) expression, and apoptosis (caspase 3 and TUNEL).
Results: There were no significant differences between the groups with respect to PCNA, MMP‐2, MMP‐14, and TUNEL positive cells. However, the expression of MMP‐9 was significantly higher in the control group than in the ZA group (P < 0.05), whereas the expression of caspase 3 was significantly lower in the control group than in the ZA group (P < 0.05).
Conclusion: These results suggest that high doses of ZA resulted in higher levels of apoptosis and lower levels of MMP‐9 in the oral epithelial cells supporting the idea of bisphosphonate treatment affects the oral mucosa.</description><identifier>ISSN: 1354-523X</identifier><identifier>EISSN: 1601-0825</identifier><identifier>DOI: 10.1111/j.1601-0825.2010.01739.x</identifier><identifier>PMID: 20860766</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Apoptosis ; Apoptosis - drug effects ; Bone Density Conservation Agents - administration & dosage ; Bone Density Conservation Agents - pharmacology ; Caspase 3 - drug effects ; Cell growth ; Cell Proliferation - drug effects ; Dentistry ; Diphosphonates - administration & dosage ; Diphosphonates - pharmacology ; Dogs ; Epithelial Cells - drug effects ; Female ; Imidazoles - administration & dosage ; Imidazoles - pharmacology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Injections, Intravenous ; Matrix Metalloproteinase 14 - drug effects ; Matrix Metalloproteinase 2 - drug effects ; Matrix Metalloproteinase 9 - drug effects ; Medical research ; Models, Animal ; Mouth Mucosa - cytology ; Mouth Mucosa - drug effects ; oral epithelial cells ; osteonecrosis of the jaws ; Proliferating Cell Nuclear Antigen - drug effects ; zoledronic acid</subject><ispartof>Oral diseases, 2011-04, Vol.17 (3), p.291-297</ispartof><rights>2010 John Wiley & Sons A/S</rights><rights>2010 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6059-62ea27d62c6cc6a58326e35272aaaf62b729652ad7f5f225458f92fb07e3ef163</citedby><cites>FETCH-LOGICAL-c6059-62ea27d62c6cc6a58326e35272aaaf62b729652ad7f5f225458f92fb07e3ef163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20860766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Allam, E</creatorcontrib><creatorcontrib>Allen, MR</creatorcontrib><creatorcontrib>Chu, T-M</creatorcontrib><creatorcontrib>Ghoneima, A</creatorcontrib><creatorcontrib>Jack Windsor, L</creatorcontrib><title>In vivo effects of zoledronic acid on oral mucosal epithelial cells</title><title>Oral diseases</title><addtitle>Oral Dis</addtitle><description>Oral Diseases (2011) 17, 291–297
Objective: Osteonecrosis of the jaw is a serious complication of bisphosphonate treatment for which the pathophysiology is unknown. The purpose of this study was to investigate whether in vivo zoledronic acid (ZA) induces alterations in cell proliferation, apoptosis, and matrix metalloproteinases (MMPs) expression in oral mucosal epithelial cells.
Methods: One‐year‐old dogs were either untreated (control group) or given high doses of intravenous ZA (ZA group) for 3 months. The doses of ZA were equivalent to those given to cancer patients, yet were administered two times more frequently (every 2 weeks). Mucosal tissues were assessed immunohistochemically for cell proliferation (proliferating cell nuclear antigen, PCNA), matrix metalloproteinase (MMP) expression, and apoptosis (caspase 3 and TUNEL).
Results: There were no significant differences between the groups with respect to PCNA, MMP‐2, MMP‐14, and TUNEL positive cells. However, the expression of MMP‐9 was significantly higher in the control group than in the ZA group (P < 0.05), whereas the expression of caspase 3 was significantly lower in the control group than in the ZA group (P < 0.05).
Conclusion: These results suggest that high doses of ZA resulted in higher levels of apoptosis and lower levels of MMP‐9 in the oral epithelial cells supporting the idea of bisphosphonate treatment affects the oral mucosa.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bone Density Conservation Agents - administration & dosage</subject><subject>Bone Density Conservation Agents - pharmacology</subject><subject>Caspase 3 - drug effects</subject><subject>Cell growth</subject><subject>Cell Proliferation - drug effects</subject><subject>Dentistry</subject><subject>Diphosphonates - administration & dosage</subject><subject>Diphosphonates - pharmacology</subject><subject>Dogs</subject><subject>Epithelial Cells - drug effects</subject><subject>Female</subject><subject>Imidazoles - administration & dosage</subject><subject>Imidazoles - pharmacology</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Injections, Intravenous</subject><subject>Matrix Metalloproteinase 14 - drug effects</subject><subject>Matrix Metalloproteinase 2 - drug effects</subject><subject>Matrix Metalloproteinase 9 - drug effects</subject><subject>Medical research</subject><subject>Models, Animal</subject><subject>Mouth Mucosa - cytology</subject><subject>Mouth Mucosa - drug effects</subject><subject>oral epithelial cells</subject><subject>osteonecrosis of the jaws</subject><subject>Proliferating Cell Nuclear Antigen - drug effects</subject><subject>zoledronic acid</subject><issn>1354-523X</issn><issn>1601-0825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNqNkUFv1DAQhS1ERUvhL6BIHDhlscexnRxAggXKSlV7AYq4jLyOTb1k48VOli2_HodtV8AJXzzyfO9pxo-QgtEZy-f5asYkZSWtQcyA5lfKFG9mu3vk5NC4n2suqlIA_3xMHqa0oplqODwgx0BrSZWUJ2S-6Iut34bCOmfNkIrgip-hs20MvTeFNr4tQl-EqLtiPZqQ8m03fri2nc-lsV2XHpEjp7tkH9_ep-Tju7cf5u_L88uzxfzVeWkkFU0pwWpQrQQjjZFa1Byk5QIUaK2dhKWCRgrQrXLCAYhK1K4Bt6TKcuuY5Kfk5d53My7XtjW2H_JYuIl-reMNBu3x707vr_Fr2CLPX1RVLBs8uzWI4fto04Brn6YVdG_DmLAWinFgEjL59B9yFcbY5-2Q5cGY4LwSmar3lIkhpWjdYRZGcQoKVzjlgVMeOAWFv4PCXZY--XOXg_AumQy82AM_fGdv_tsYL98spirry73ep8HuDnodv6FUXAm8ujjD-jX7wi-uPqHivwDH2LAc</recordid><startdate>201104</startdate><enddate>201104</enddate><creator>Allam, E</creator><creator>Allen, MR</creator><creator>Chu, T-M</creator><creator>Ghoneima, A</creator><creator>Jack Windsor, L</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>7QP</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201104</creationdate><title>In vivo effects of zoledronic acid on oral mucosal epithelial cells</title><author>Allam, E ; Allen, MR ; Chu, T-M ; Ghoneima, A ; Jack Windsor, L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6059-62ea27d62c6cc6a58326e35272aaaf62b729652ad7f5f225458f92fb07e3ef163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Bone Density Conservation Agents - administration & dosage</topic><topic>Bone Density Conservation Agents - pharmacology</topic><topic>Caspase 3 - drug effects</topic><topic>Cell growth</topic><topic>Cell Proliferation - drug effects</topic><topic>Dentistry</topic><topic>Diphosphonates - administration & dosage</topic><topic>Diphosphonates - pharmacology</topic><topic>Dogs</topic><topic>Epithelial Cells - drug effects</topic><topic>Female</topic><topic>Imidazoles - administration & dosage</topic><topic>Imidazoles - pharmacology</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Injections, Intravenous</topic><topic>Matrix Metalloproteinase 14 - drug effects</topic><topic>Matrix Metalloproteinase 2 - drug effects</topic><topic>Matrix Metalloproteinase 9 - drug effects</topic><topic>Medical research</topic><topic>Models, Animal</topic><topic>Mouth Mucosa - cytology</topic><topic>Mouth Mucosa - drug effects</topic><topic>oral epithelial cells</topic><topic>osteonecrosis of the jaws</topic><topic>Proliferating Cell Nuclear Antigen - drug effects</topic><topic>zoledronic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Allam, E</creatorcontrib><creatorcontrib>Allen, MR</creatorcontrib><creatorcontrib>Chu, T-M</creatorcontrib><creatorcontrib>Ghoneima, A</creatorcontrib><creatorcontrib>Jack Windsor, L</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oral diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Allam, E</au><au>Allen, MR</au><au>Chu, T-M</au><au>Ghoneima, A</au><au>Jack Windsor, L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo effects of zoledronic acid on oral mucosal epithelial cells</atitle><jtitle>Oral diseases</jtitle><addtitle>Oral Dis</addtitle><date>2011-04</date><risdate>2011</risdate><volume>17</volume><issue>3</issue><spage>291</spage><epage>297</epage><pages>291-297</pages><issn>1354-523X</issn><eissn>1601-0825</eissn><abstract>Oral Diseases (2011) 17, 291–297
Objective: Osteonecrosis of the jaw is a serious complication of bisphosphonate treatment for which the pathophysiology is unknown. The purpose of this study was to investigate whether in vivo zoledronic acid (ZA) induces alterations in cell proliferation, apoptosis, and matrix metalloproteinases (MMPs) expression in oral mucosal epithelial cells.
Methods: One‐year‐old dogs were either untreated (control group) or given high doses of intravenous ZA (ZA group) for 3 months. The doses of ZA were equivalent to those given to cancer patients, yet were administered two times more frequently (every 2 weeks). Mucosal tissues were assessed immunohistochemically for cell proliferation (proliferating cell nuclear antigen, PCNA), matrix metalloproteinase (MMP) expression, and apoptosis (caspase 3 and TUNEL).
Results: There were no significant differences between the groups with respect to PCNA, MMP‐2, MMP‐14, and TUNEL positive cells. However, the expression of MMP‐9 was significantly higher in the control group than in the ZA group (P < 0.05), whereas the expression of caspase 3 was significantly lower in the control group than in the ZA group (P < 0.05).
Conclusion: These results suggest that high doses of ZA resulted in higher levels of apoptosis and lower levels of MMP‐9 in the oral epithelial cells supporting the idea of bisphosphonate treatment affects the oral mucosa.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>20860766</pmid><doi>10.1111/j.1601-0825.2010.01739.x</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oral diseases, 2011-04, Vol.17 (3), p.291-297 |
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| source | Wiley-Blackwell Read & Publish Collection |
| subjects | Animals Apoptosis Apoptosis - drug effects Bone Density Conservation Agents - administration & dosage Bone Density Conservation Agents - pharmacology Caspase 3 - drug effects Cell growth Cell Proliferation - drug effects Dentistry Diphosphonates - administration & dosage Diphosphonates - pharmacology Dogs Epithelial Cells - drug effects Female Imidazoles - administration & dosage Imidazoles - pharmacology Immunohistochemistry In Situ Nick-End Labeling Injections, Intravenous Matrix Metalloproteinase 14 - drug effects Matrix Metalloproteinase 2 - drug effects Matrix Metalloproteinase 9 - drug effects Medical research Models, Animal Mouth Mucosa - cytology Mouth Mucosa - drug effects oral epithelial cells osteonecrosis of the jaws Proliferating Cell Nuclear Antigen - drug effects zoledronic acid |
| title | In vivo effects of zoledronic acid on oral mucosal epithelial cells |
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