Autocrine growth factors in human periodontal ligament cells cultured on enamel matrix derivative

Objective: Enamel extracellular matrix proteins in the form of the enamel m atrix derivative EMDOGAIN(R) (EMD) have been successfully employed to mimic natural cementogenesis to restore fully functional periodontal ligament, c ementum and alveolar bone in patients with severe periodontitis. When appli ed to denuded root surfaces EMD forms a matrix that locally facilitates reg enerative responses in the adjacent periodontal tissues. The cellular mecha nism(s), e.g. autocrine growth factors, extracellular matrix synthesis and cell growth, underlying PDL regeneration with EMD is however poorly investi gated. Material and Methods: Human periodontal ligament (PDL) cells were cultured on EMD and monitored for cellular attachment rate, proliferation, DNA repli cation and metabolism. Furthermore, intracellular cyclic-AMP levels and aut ocrine production of selected growth factors were monitored by immunologica l assays. Controls included PDL and epithelial cells in parallel cultures. Results: PDL cell attachment rate, growth and metabolism were all significa ntly increased when EMD was present in cultures. Also, cells exposed to EMD showed increased intracellular cAMP signalling and autocrine production of TGF-beta1, IL-6 and PDGF AB when compared to controls. Epithelial cells in creased cAMP and PDGF AB secretion when EMD was present, but proliferation and growth were inhibited. Conclusion: Cultured PDL cells exposed to EMD increase attachment rate, gro wth rate and metabolism, and subsequently release several growth factors in to the medium. The cellular interaction with EMD generates an intracellular cAMP signal, after which cells secrete TGF-beta1, IL-6 and PDGF AB. Epithe lial cell growth however, is inhibited by the same signal. This suggest tha t EMD favours mesenchymal cell growth over epithelium, and that autocrine g rowth factors released by PDL cells exposed to EMD contribute to periodonta l healing and regeneration in a process mimicking natural root development.