Document Detail


In vivo effects of zoledronic acid on oral mucosal epithelial cells.
MedLine Citation:
PMID:  20860766     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
E Allam; Mr Allen; T-M Chu; A Ghoneima; L Jack Windsor
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-23
Journal Detail:
Title:  Oral diseases     Volume:  17     ISSN:  1601-0825     ISO Abbreviation:  Oral Dis     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-14     Completed Date:  2011-07-26     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  9508565     Medline TA:  Oral Dis     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  291-7     Citation Subset:  D    
Copyright Information:
© 2010 John Wiley & Sons A/S.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Bone Density Conservation Agents / administration & dosage,  pharmacology*
Caspase 3 / drug effects
Cell Proliferation / drug effects
Diphosphonates / administration & dosage,  pharmacology*
Dogs
Epithelial Cells / drug effects
Female
Imidazoles / administration & dosage,  pharmacology*
Immunohistochemistry
In Situ Nick-End Labeling
Injections, Intravenous
Matrix Metalloproteinase 14 / drug effects
Matrix Metalloproteinase 2 / drug effects
Matrix Metalloproteinase 9 / drug effects
Models, Animal
Mouth Mucosa / cytology,  drug effects*
Proliferating Cell Nuclear Antigen / drug effects
Grant Support
ID/Acronym/Agency:
C06RR10601/RR/NCRR NIH HHS; R21 DE019686/DE/NIDCR NIH HHS; R21 DE019686-02/DE/NIDCR NIH HHS; R21-DE019686/DE/NIDCR NIH HHS; S10-RR023710/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Bone Density Conservation Agents; 0/Diphosphonates; 0/Imidazoles; 0/Proliferating Cell Nuclear Antigen; 118072-93-8/zoledronic acid; EC 3.4.22.-/Caspase 3; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9; EC 3.4.24.80/Matrix Metalloproteinase 14
Comments/Corrections

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