Mast Cell Subpopulations in Gingival Overgrowth Induced by Immunosuppressive and Nifedipine Medication

Nurmenniemi, Petri K.; Pernu, Hannu; Knuuttila, Matti

doi:10.1902/jop.2004.75.7.933

Cited by 13 publications

(17 citation statements)

References 26 publications

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“…Similar to gingival overgrowth and oral cancer (Flynn et al 1991;Soory and Suchak 2001;Iamaroon et al 2003;Nurmenniemi et al 2004;Mohtasham et al 2010;Pyziak et al 2013), increased levels of degranulated mast cells and macrophages are associated with neurofibromas. Analysis of initial data suggests that the macrophages in NF1 tissues are not principally synthetic macrophages (Prada et al 2013), but additional studies are required.…”

Section: Gingival Overgrowth and Cancermentioning

confidence: 99%

Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth

Trackman

Kantarcı²

2015

J Dent Res

133

109

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Drug-induced gingival overgrowth is a tissue-specific condition and is estimated to affect approximately one million North Americans. Lesions occur principally as side-effects from phenytoin, nifedipine, or ciclosporin therapy in approximately half of the people who take these agents. Due to new indications for these drugs, their use continues to grow. Here, we review the molecular and cellular characteristics of human gingival overgrowth lesions and highlight how they differ considerably as a function of the causative drug. Analyses of molecular signaling pathways in cultured human gingival fibroblasts have provided evidence for their unique aspects compared with fibroblasts from the lung and kidney. These findings provide insights into both the basis for tissue specificity and into possible therapeutic opportunities which are reviewed here. Although ciclosporin-induced gingival overgrowth lesions exhibit principally the presence of inflammation and little fibrosis, nifedipine-and especially phenytoin-induced lesions are highly fibrotic. The increased expression of markers of gingival fibrosis, particularly CCN2 [also known as connective tissue growth factor (CTGF)], markers of epithelial to mesenchymal transition, and more recently periostin and members of the lysyl oxidase family of enzymes have been documented in phenytoin or nifedipine lesions. Some oral fibrotic conditions such as leukoplakia and oral submucous fibrosis, after subsequent additional genetic damage, can develop into oral cancer. Since many pathways are shared, the study of gingival fibrosis and comparisons with characteristics and molecular drivers of oral cancer would likely enhance understandings and functional roles of molecular drivers of these oral pathologies.

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Section: Gingival Overgrowth and Cancermentioning

confidence: 99%

Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth

Trackman

Kantarcı²

2015

J Dent Res

133

109

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“…Several in vitro studies have pointed out the potential role of mast cells inducing gingival fibroblast proliferation and collagen synthesis [65]. A recently published study demonstrated that mast cell tryptase and chymase enzymes were expressed significantly higher in DIGO tissues compared to healthy gingiva and may contribute to alterations in basement membranes [66]. In addition, tryptase can interact with a number of cell types and has been shown to be mitogenic for fibroblasts [67] and epithelial cells [68].…”

Section: Mast Cell Proteasesmentioning

confidence: 99%

The Possible Potential Therapeutic Targets for Drug Induced Gingival Overgrowth

Subramani

Rathnavelu

Alitheen

2013

Mediators of Inflammation

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Gingival overgrowth is a side effect of certain medications. The most fibrotic drug-induced lesions develop in response to therapy with phenytoin, the least fibrotic lesions are caused by cyclosporin A, and the intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, activated gingival fibroblasts synthesize and remodel newly created extracellular matrix. Proteins such as transforming growth factor (TGF), endothelin-1 (ET-1), angiotensin II (Ang II), connective tissue growth factor (CCN2/CTGF), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF) appear to act in a network that contributes to the development of gingival fibrosis. Since inflammation is the prerequisite for gingival overgrowth, mast cells and its protease enzymes also play a vital role in the pathogenesis of gingival fibrosis. Drugs targeting these proteins are currently under consideration as antifibrotic treatments. This review summarizes recent observations concerning the contribution of TGF-β, CTGF, IGF, PDGF, ET-1, Ang II, and mast cell chymase and tryptase enzymes to fibroblast activation in gingival fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of drug-induced gingival overgrowth.

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“…It is now thought that mast cell-specific proteases (chymase and tryptase) represent the main criterion of differentiation: mast cells containing only tryptase (MC T ) can be distinguished from those containing both tryptase and chymase (MC TC ). Importantly, in several models both MC T and MC TC were present and directly involved in gingival fibrosis [8, 12]. Chronic periodontitis and fibrosis involve a common sequence of events requiring the interaction of endothelial cells with infiltrating mast cell.…”

Section: Gingival Mast Cells and Fibrosismentioning

confidence: 99%

“…Mast cells synthesize renin and release during degranulation that can generate Ang II from Ang I [21, 30]. Nurmenniemi et al 2004 have demonstrated the augmented mast cell and its enzyme chymase and tryptase in healthy human gingival connective tissue [8]. Despite the great number of studies on mast cell populations, at the present time studies regarding the stimulation of local RAS by mast cells in human gingiva are very few.…”

Section: Renin Angiotensin System and Mast Cellmentioning

confidence: 99%

“…Furthermore, the presence of various degrees of gingival inflammation is one reason for difficulty in the accurate assessment of DIGO, because inflammation acts as an exacerbation factor of gingival overgrowth. At the cellular level, gingival fibrogenesis is initiated by several mediators which induce the recruitment of a large number of inflammatory cells, including mast cells (MCs) [8]. MCs are tissue-specific multifunctional cells, derived from hematopoietic progenitor in bone marrow.…”

Section: Introductionmentioning

confidence: 99%

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Influence of Mast Cells in Drug-Induced Gingival Overgrowth

Subramani

Rathnavelu

Yeap

et al. 2013

Mediators of Inflammation

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Mast cells (MCs) are multifunctional effector cells that were originally thought to be involved in allergic disorders. Now it is known that they contain an array of mediators with a multitude of effects on many other cells. MCs have become a recent concern in drug-induced gingival overgrowth (DIGO), an unwanted outcome of systemic medication. Most of the studies have confirmed the significant presence of inflammation as a prerequisite for the overgrowth to occur. The inflammatory changes within the gingival tissue appear to influence the interaction between the inducing drug and the fibroblast activity. The development of antibodies to MC-specific enzymes, tryptase and chymase, has facilitated the study of mast cells in DIGO. Many immunohistochemical studies involving MCs have been conducted; as a result, DIGO tissues are found to have increased the number of MCs in the gingiva, especially in the area of fibrosis. At the cellular level, gingival fibrogenesis is initiated by several mediators which induce the recruitment of a large number of inflammatory cells, including MCs. The purpose of this paper is to access the roles played by MCs in gingival overgrowth to hypothesize a relationship between these highly specialized cells in the pathogenesis of DIGO.

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Mast Cell Subpopulations in Gingival Overgrowth Induced by Immunosuppressive and Nifedipine Medication

Cited by 13 publications

References 26 publications

Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth

Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth

The Possible Potential Therapeutic Targets for Drug Induced Gingival Overgrowth

Influence of Mast Cells in Drug-Induced Gingival Overgrowth

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