Emdogain® in carcinogenesis: a systematic review of in vitro studies

Abstract

Emdogain is a commercial product of unknown composition and is clinically used to induce periodontal regeneration. This study aims to review current knowledge of the in vitro effects of Emdogain on oral tissues and, in particular, factors related to carcinoma. A systematic approach was used to review studies from the Embase and Pubmed databases; a total of 76 studies were included. These comprised in vitro studies of the cytokines in, or regulated by, Emdogain and assays designed to study the effects of EMD on human cells in oral tissues or malignant cells. Several studies have shown that EMD regulates the proliferation, migration, adhesion, gene expression, and cytokine production of (pre-)osteoblasts, periodontal fibroblasts, and gingival fibroblasts. However, the effects of EMD on malignant oral cells are not well understood. EMD seems to have broad regulatory effects on malignant cells and on several carcinoma-related factors. Evidence suggests that patients with premalignant or malignant mucosal lesions should not be treated with EMD. (J Oral Sci 52, 1-11, 2010)

Effects of enamel matrix proteins on adherence, proliferation and migration of epithelial cells: A real-time in vitro study

“…Previous studies conducted on cervical cancer cells indicated that EMD has an inhibitory effect on epithelial cells (13,27). Lyngstadaas et al (15) showed that HeLa cells growing in the presence of EMD exhibited a highly increased intracellular level of cyclic adenosine monophosphate compared with controls.…”

“…Results concerning the influence of EMD on oral epithelial cells are particularly ambiguous; EMD was determined to have an anti-proliferative effect on epithelial cells (12,13), but numerous clinicians have observed accelerated epithelial soft-tissue healing upon intrasurgical application of EMD (26–29). It has been suggested that EMD may induce alterations in malignant mucosal tissue, which implies that patients with pre-malignant or malignant mucosal lesions should not be treated with EMD (27). …”

Potential usefulness of enamel matrix derivative in skin and mucosal injury treatment

“…The results of research on the effects of EMD on oral epithelial cells are ambigu- ous. EMD has been shown to decrease the proliferation of epithelial cells [27,28], but in many clinical trials, the acceleration of epithelial healing after intraoperative EMD use was observed [29][30][31][32]. It is suggested that EMD may induce malignant lesions in the mucosa, which means that patients with pre-cancerous or malignant lesions on the mucosa should not be treated with EMD [30].…”

Enamel matrix proteins exhibit growth factor activity: A review of evidence at the cellular and molecular levels

“…Kawase et al (46) postulated that EMD reduced DNA synthesis, suggesting that a reduction in epithelial cell growth could be mediated by TGF-β-like activity. EMD and TGF-β are also able to stimulate the production of matrix metalloproteinases (MMPs), which are crucial in tumorigenesis and in benign keratinocytes (27).…”

“…While EMD presents a number of growth factor-like effects, it is the TGF-β activity that is predominately known (23)(24)(25)(26). EMD has also been reported to contain other cytokines, such as a BMP-like growth factor and bone sialoprotein (BSP)-like molecules (27,28).…”