Autocrine growth factors in human periodontal ligament cells cultured on enamel matrix derivative.
OBJECTIVE
Enamel extracellular matrix proteins in the form of the enamel matrix derivative EMDOGAIN (EMD) have been successfully employed to mimic natural cementogenesis to restore fully functional periodontal ligament, cementum and alveolar bone in patients with severe periodontitis. When applied to denuded root surfaces EMD forms a matrix that locally facilitates regenerative responses in the adjacent periodontal tissues. The cellular mechanism(s), e.g. autocrine growth factors, extracellular matrix synthesis and cell growth, underlying PDL regeneration with EMD is however poorly investigated.


METHODS
Human periodontal ligament (PDL) cells were cultured on EMD and monitored for cellular attachment rate, proliferation, DNA replication and metabolism. Furthermore, intracellular cyclic-AMP levels and autocrine production of selected growth factors were monitored by immunological assays. Controls included PDL and epithelial cells in parallel cultures.


RESULTS
PDL cell attachment rate, growth and metabolism were all significantly 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 increased cAMP and PDGF AB secretion when EMD was present, but proliferation and growth were inhibited.


CONCLUSIONS
Cultured PDL cells exposed to EMD increase attachment rate, growth rate and metabolism, and subsequently release several growth factors into the medium. The cellular interaction with EMD generates an intracellular cAMP signal, after which cells secrete TGF-beta1, IL-6 and PDGF AB. Epithelial cell growth however, is inhibited by the same signal. This suggest that EMD favours mesenchymal cell growth over epithelium, and that autocrine growth factors released by PDL cells exposed to EMD contribute to periodontal healing and regeneration in a process mimicking natural root development.
Lyngstadaas
S P
SP
Department Research and Development, Biora AB, Malmö, Sweden. petter.lyngstadaas@biora.com
Lundberg
E
E
Ekdahl
H
H
Andersson
C
C
Gestrelius
S
S
D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D000242:Cyclic AMP / Q000096:biosynthesis; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D006133:Growth Substances / Q000096:biosynthesis*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D012038:Regeneration / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D003470:Culture Media; D003746:Dental Enamel Proteins; D006133:Growth Substances; D007375:Interleukin-1; D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; C109069:enamel matrix proteins; C095477:platelet-derived growth factor AB; D000242:Cyclic AMP