Connective Tissue Metabolism and Gingival Overgrowth

Abstract

Gingival overgrowth occurs mainly as a result of certain anti-seizure, immunosuppressive, or antihypertensive drug therapies. Excess gingival tissues impede oral function and are disfiguring. Effective oral hygiene is compromised in the presence of gingival overgrowth, and it is now recognized that this may have negative implications for the systemic health of affected patients. Recent studies indicate that cytokine balances are abnormal in drug-induced forms of gingival overgrowth. Data supporting molecular and cellular characteristics that distinguish different forms of gingival overgrowth are summarized, and aspects of gingival fibroblast extracellular matrix metabolism that are unique to gingival tissues and cells are reviewed. Abnormal cytokine balances derived principally from lymphocytes and macrophages, and unique aspects of gingival extracellular matrix metabolism, are elements of a working model presented to facilitate our gaining a better understanding of mechanisms and of the tissue specificity of gingival overgrowth.

Epithelial to Mesenchymal Transition in Gingival Overgrowth

“…3,4 It is interesting that a classic feature of gingival overgrowth is that epithelial rete pegs extend deep into the connective tissue compared with normal tissues, and all forms of gingival overgrowth lesions contain fibrotic or expanded connective tissues with characteristic levels of inflammation. 5 Moreover, we have observed elevated expressions of CCN2/ CTGF in both epithelial and connective tissue cells in phenytoin-induced gingival overgrowth tissues. 6 CCN2/CTGF is considered to be a marker of fibroblastic mesenchymal cells and is increased in cells undergoing epithelial to mesenchymal transition (EMT) in development, and in fibrosis.…”

Molecular and Clinical Aspects of Drug-induced Gingival Overgrowth

“…As already amply summarized by us and others, gingival overgrowth leads to compromised quality of life for patients, and can lead to indirect negative effects on systemic health (Hassell and Hefti 1991;Marshall and Bartold 1999;Seymour et al 2000;Trackman and Kantarci 2004;Wright et al 2005;Bharti and Bansal 2013). Present and future novel cellular mechanisms discovered in analyses of gingival overgrowth may have relevance to other oral diseases, most notably oral cancer, and neurofibromatosis-1, with the latter often accompanied by gingival overgrowth and tongue lesions which can progress to oral cancer (Cunha et al 2004;Jouhilahti et al 2012).…”

“…Non-surgical therapies to treat gingival overgrowth and stabilize the long-term outcomes are needed to alleviate suffering for those who are adversely affected. In addition to drug-induced gingival overgrowth, inherited and idiopathic forms of this condition, while rare, occur and have been reviewed previously (Hassell and Hefti 1991;Marshall and Bartold 1999;Seymour et al 2000;Trackman and Kantarci 2004;Bharti and Bansal 2013). Although progress in the clinical management of human gingival overgrowth has been made in relatively affluent societies, approaches of drug substitutions and careful dose adjustments are not universally practiced by physicians worldwide, and this contributes to the global public health impact of gingival overgrowth (Bharti and Bansal 2013).…”

Gingivitis in Children and Adolescents

“…Patients on these medications develop varying degrees of gingival overgrowth (Trackman & Kantaki, 2004;Cury et al, 2009). Gingival enlargement is the most significant oral finding (Robbins, 2009) and can occour in up to 50% of patients taking Phenytoin (Thomason et al, 1992).…”