On the Cellular and Molecular Mechanisms of Drug-Induced Gingival Overgrowth.
| Title: | On the Cellular and Molecular Mechanisms of Drug-Induced Gingival Overgrowth. |
|---|---|
| Authors: | Ramírez-Rámiz A; Department of Odontostomatology. Faculty of Medicine and Health Sciences. University of Barcelona, Barcelona, Spain.; Brunet-LLobet L; Department of Dentistry. Hospital Universitari Sant Joan de Déu. University of Barcelona, Barcelona, Spain.; Lahor-Soler E; Department of Odontostomatology. Faculty of Medicine and Health Sciences. University of Barcelona, Barcelona, Spain.; Miranda-Rius J; Department of Odontostomatology. Faculty of Medicine and Health Sciences. University of Barcelona, Barcelona, Spain. |
| Source: | The open dentistry journal [Open Dent J] 2017 Jul 31; Vol. 11, pp. 420-435. Date of Electronic Publication: 2017 Jul 31 (Print Publication: 2017). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Bentham Open Country of Publication: United Arab Emirates NLM ID: 101480503 Publication Model: eCollection Cited Medium: Print ISSN: 1874-2106 (Print) Linking ISSN: 18742106 NLM ISO Abbreviation: Open Dent J Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Publication: Saif Zone, Sharjah, U.A.E. : Bentham Open; Original Publication: [Hilversum : Bentham Science Publishers, 2007]- |
| Abstract: | Introduction: Gingival overgrowth has been linked to multiple factors such as adverse drug effects, inflammation, neoplastic processes, and hereditary gingival fibromatosis. Drug-induced gingival overgrowth is a well-established adverse event. In early stages, this gingival enlargement is usually located in the area of the interdental papilla. Histologically, there is an increase in the different components of the extracellular matrix.; Objective: The aim of this manuscript is to describe and analyze the different cellular and molecular agents involved in the pathogenesis of Drug-induced gingival overgrowth.; Method: A literature search of the MEDLINE/PubMed database was conducted to identify the mechanisms involved in the process of drug-induced gingival overgrowth, with the assistance of a research librarian. We present several causal hypotheses and discuss the advances in the understanding of the mechanisms that trigger this gingival alteration.; Results: In vitro studies have revealed phenotypic cellular changes in keratinocytes and fibroblasts and an increase of the extracellular matrix with collagen and glycosaminoglycans. Drug-induced gingival overgrowth confirms the key role of collagenase and integrins, membrane receptors present in the fibroblasts, due to their involvement in the catabolism of collagen. The three drug categories implicated: calcineuron inhibitors (immunosuppressant drugs), calcium channel blocking agents and anticonvulsant drugs appear to present a multifactorial pathogenesis with a common molecular action: the blockage of the cell membrane in the Ca2+/Na+ ion flow. The alteration of the uptake of cellular folic acid, which depends on the regulated channels of active cationic transport and on passive diffusion, results in a dysfunctional degradation of the connective tissue. Certain intermediate molecules such as cytokines and prostaglandins play a role in this pathological mechanism. The concomitant inflammatory factor encourages the appearance of fibroblasts, which leads to gingival fibrosis. Susceptibility to gingival overgrowth in some fibroblast subpopulations is due to phenotypic variability and genetic polymorphism, as shown by the increase in the synthesis of molecules related to the response of the gingival tissue to inducing drugs. The authors present a diagram depicting various mechanisms involved in the pathogenesis of drug-induced gingival overgrowth.; Conclusion: Individual predisposition, tissue inflammation, and molecular changes in response to the inducing drug favor the clinical manifestation of gingival overgrowth. |
| References: | J Periodontal Res. 1996 Nov;31(8):545-55. (PMID: 8971653); J Periodontol. 1997 Apr;68(4):375-80. (PMID: 9150043); J Oral Pathol. 1987 Mar;16(3):129-34. (PMID: 3114451); J Clin Periodontol. 1996 Jul;23(7):628-34. (PMID: 8841894); J Periodontol. 2005 Dec;76(12):2267-75. (PMID: 16332239); Eur J Clin Invest. 2001 Sep;31(9):781-8. (PMID: 11589720); J Periodontol. 2002 Feb;73(2):145-52. (PMID: 11895278); J Periodontol. 2002 Aug;73(8):892-9. (PMID: 12211499); J Oral Pathol Med. 1995 Feb;24(2):72-7. (PMID: 7745545); J Periodontol. 2007 Feb;78(2):304-14. (PMID: 17274720); J Periodontal Res. 2007 Oct;42(5):443-9. (PMID: 17760822); J Clin Periodontol. 2008 May;35(5):371-8. (PMID: 18355347); J Periodontol. 2005 Jun;76(6):941-50. (PMID: 15948689); Br J Pharmacol. 1992 Jul;106(3):574-8. (PMID: 1504741); Arch Oral Biol. 1994 Feb;39(2):99-104. (PMID: 8185505); Am J Respir Cell Mol Biol. 1999 Dec;21(6):658-65. (PMID: 10572062); J Periodontal Res. 2006 Aug;41(4):297-302. (PMID: 16827723); Oral Dis. 2004 Mar;10(2):87-93. (PMID: 14996278); J Periodontal Res. 2006 Aug;41(4):316-21. (PMID: 16827726); J Periodontol. 2013 Oct;84(10 ):1469-75. (PMID: 23173828); J Can Dent Assoc. 2003 Apr;69(4):236-41. (PMID: 12662462); J Periodontal Res. 1992 Sep;27(5):499-505. (PMID: 1403578); G Ital Cardiol. 1985 May;15(5):556-7. (PMID: 4054493); J Periodontal Res. 2007 Dec;42(6):580-8. (PMID: 17956473); J Periodontal Res. 1996 Feb;31(2):131-4. (PMID: 8708940); J Periodontol. 2002 Nov;73(11):1313-22. (PMID: 12479636); Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Oct;116(4):447-54. (PMID: 24035111); J Periodontol. 2001 Aug;72(8):1078-83. (PMID: 11525441); J Cell Biochem. 2006 May 15;98(2):409-20. (PMID: 16440322); J Oral Pathol Med. 2004 Jul;33(6):346-53. (PMID: 15200483); J Clin Invest. 2007 Mar;117(3):524-9. (PMID: 17332879); Toxicol Mech Methods. 2015 Feb;25(2):98-104. (PMID: 25418342); J Periodontal Res. 1999 Jan;34(1):7-15. (PMID: 10086881); Front Cell Infect Microbiol. 2015 Dec 01;5:87. (PMID: 26649282); J Dent Res. 2005 Dec;84(12):1183-6. (PMID: 16304451); J Periodontol. 1997 Jan;68(1):73-83. (PMID: 9029455); J Periodontol. 2009 Oct;80(10):1638-47. (PMID: 19792854); J Periodontol. 2001 Jul;72(7):921-31. (PMID: 11495141); J Cell Biochem. 1991 Jun;46(2):152-65. (PMID: 1655819); J Clin Periodontol. 2005 Mar;32(3):273-9. (PMID: 15766370); J Clin Periodontol. 2005 Mar;32(3):294-8. (PMID: 15766373); J Periodontal Res. 2004 Oct;39(5):320-6. (PMID: 15324353); Crit Rev Oral Biol Med. 1997;8(3):253-68. (PMID: 9260043); J Periodontol. 2002 Aug;73(8):861-7. (PMID: 12211494); J Clin Periodontol. 2004 Oct;31(10):863-8. (PMID: 15367190); Am J Pathol. 2002 Dec;161(6):2047-52. (PMID: 12466121); Transplant Proc. 2008 Jun;40(5):1425-8. (PMID: 18589122); J Dent Res. 2013 Nov;92(11):1022-8. (PMID: 24004653); Rom J Morphol Embryol. 2012;53(1):161-5. (PMID: 22395516); J Periodontol. 2001 Jun;72(6):745-52. (PMID: 11453236); Comp Biochem Physiol C Toxicol Pharmacol. 2002 Aug;132(4):451-60. (PMID: 12223201); J Periodontol. 2008 Jan;79(1):114-22. (PMID: 18166100); Growth Factors. 2010 Feb;28(1):24-33. (PMID: 19886734); Eur J Clin Pharmacol. 2013 Mar;69(3):385-93. (PMID: 22886152); Eur J Orthod. 2011 Dec;33(6):705-11. (PMID: 21389074); Oral Surg Oral Med Oral Pathol. 1988 Feb;65(2):183-5. (PMID: 3422722); J Periodontol. 2010 Sep;81(9):1250-5. (PMID: 20397903); Head Face Med. 2006 May 19;2:13. (PMID: 16712728); Dent Res J (Isfahan). 2015 Nov-Dec;12(6):499-506. (PMID: 26759584); J Clin Periodontol. 1997 Mar;24(3):180-2. (PMID: 9083902); J Cell Biol. 2007 Dec 17;179(6):1311-23. (PMID: 18086923); J Periodontol. 1994 Jul;65(7):666-70. (PMID: 7608842); J Periodontol. 2003 Apr;74(4):437-45. (PMID: 12747447); J Periodontol. 1994 Jul;65(7):671-5. (PMID: 7608843); Crit Rev Oral Biol Med. 2004 Jun 04;15(3):165-75. (PMID: 15187034); Arch Oral Biol. 2008 Nov;53(11):1042-9. (PMID: 18471799); Oral Dis. 2015 Jan;21(1):e51-61. (PMID: 24893951); J Periodontal Res. 2013 Jun;48(3):386-91. (PMID: 23106187); J Periodontal Res. 2012 Dec;47(6):776-82. (PMID: 22897219); J Periodontol. 2003 Nov;74(11):1625-33. (PMID: 14682659); J Oral Pathol. 1982 Aug;11(4):310-7. (PMID: 6286912); J Periodontol. 2006 Apr;77(4):647-56. (PMID: 16584346); J Periodontal Res. 2008 Dec;43(6):665-72. (PMID: 18702631); J Clin Periodontol. 1996 Jul;23(7):635-40. (PMID: 8841895); J Periodontol. 2007 Feb;78(2):290-5. (PMID: 17274718); Eur J Pharmacol. 2001 Mar 9;415(1):95-103. (PMID: 11245857); J Dent Res. 2007 Jan;86(1):25-34. (PMID: 17189459); Drug Saf. 1996 Sep;15(3):219-31. (PMID: 8879976); J Clin Diagn Res. 2015 Aug;9(8):ZC92-4. (PMID: 26436057); J Periodontol. 2002 Nov;73(11):1323-30. (PMID: 12479637); J Periodontol. 1996 Mar;67(3):264-70. (PMID: 8708959); J Cell Physiol. 2000 Mar;182(3):351-8. (PMID: 10653601); J Periodontol. 1996 Mar;67(3):271-8. (PMID: 8708960); J Periodontal Res. 2003 Oct;38(5):533-7. (PMID: 12941079); J Periodontol. 2001 May;72(5):605-11. (PMID: 11394395); J Cell Sci. 1993 Nov;106 ( Pt 3):869-78. (PMID: 8308069); J Periodontol. 2001 Feb;72(2):167-73. (PMID: 11288789); J Clin Periodontol. 1998 Aug;25(8):640-6. (PMID: 9722268); J Dent Res. 2007 Sep;86(9):888-92. (PMID: 17720861); J Periodontal Res. 2007 Apr;42(2):144-51. (PMID: 17305873); J Clin Periodontol. 2006 Jul;33(7):510-6. (PMID: 16820039); Am J Pathol. 2010 Jul;177(1):208-18. (PMID: 20489142); J Periodontol. 1992 Jun;63(6):548-53. (PMID: 1625155); J Dent Res. 2015 Apr;94(4):540-6. (PMID: 25680368); J Periodontol. 1985 Apr;56(4):211-5. (PMID: 3858503); J Oral Sci. 2010 Mar;52(1):55-62. (PMID: 20339233); J Clin Periodontol. 1983 May;10(3):237-46. (PMID: 6575979); Semin Liver Dis. 2010 May;30(2):195-204. (PMID: 20422501); Oral Dis. 2006 Mar;12(2):156-62. (PMID: 16476037); J Periodontal Res. 2007 Dec;42(6):553-8. (PMID: 17956469); J Periodontol. 2001 Feb;72(2):160-6. (PMID: 11288788); Clin Pharmacol Ther. 2006 Jan;79(1):62-71. (PMID: 16413242); Int J Biochem Cell Biol. 2015 May;62:80-7. (PMID: 25747904); Rom J Morphol Embryol. 2010;51(3):515-9. (PMID: 20809029); J Periodontol. 1992 May;63(5):397-404. (PMID: 1527683); J Clin Periodontol. 2000 Jul;27(7):506-12. (PMID: 10914892); J Periodontol. 2004 Jul;75(7):933-8. (PMID: 15341350) |
| Contributed Indexing: | Keywords: Cellular cultures; Collagen; Drug-induced gingival overgrowth; Fibroblast; Growth factor |
| Entry Date(s): | Date Created: 20170905 Latest Revision: 20220321 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5564016 |
| DOI: | 10.2174/1874210601711010420 |
| PMID: | 28868093 |
| Database: | MEDLINE |
Journal Article