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Free keywords:
HUMAN PERIODONTAL-LIGAMENT; BONE MORPHOGENETIC PROTEIN-7; GINGIVAL
CREVICULAR FLUID; MESENCHYMAL STEM-CELLS; OSTEOGENIC DIFFERENTIATION;
INFLAMMATORY MEDIATORS; EP2/EP4 SUBTYPES; PGE(2) RECEPTORS;
PROSTAGLANDIN-E; GROWTH-FACTORBiochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism; Periodontitis; Scaffold; hTERT; BMP-7; Mesenchymal stem cell;
Periodontal ligament stem cell;
Abstract:
Regenerative therapies of pathogenic tissue defects are gaining increasing importance in periodontology. Among others, the osteogenic effect of BMP-7 seems to play a major role in the development of teeth and alveolar bone. Human periodontal ligament stem cells (hPDLSC), as well as human mesenchymal stem cells (hMSC), show the ability to differentiate into various types of tissues. Regarding prostaglandin E2, many studies have confirmed that it is involved in the inflammation associated to periodontitis stimulating osteoclasts, which ultimately leads to resorption of tooth supporting bone. Herein, we aimed to investigate how PGE2 influences regenerative processes.
The influence of PGE2 and BMP-7 on the osteogenic differentiation of hMSC and hPDLSC was determined in a 3D cell culture model using qRT-PCR, immunocytochemistry and REM. BMP-7 enhanced the expression of osteogenic markers in hMSC and lowered it in hPDLSC-TERT. BMP-7 had a lower osteogenic effect on hPDLSC-hTERT than on hMSC, while PGE2 decreases the osteogenic differentiation in both cell types, thus, inhibiting anabolic processes. Both cell types presented good proliferation and adhesion onto the scaffolds. The well developed structural morphology and the support of osteogenic differentiation suggest that the scaffolds are potential candidate materials for bone regeneration. The positivity for Cap in hPDLSC and more in hMSC immunostaining samples indicates the initiation of neocementogenesis as part of periodontal regeneration.
In conclusion, BMP7, in particular combined with MSC, seems to have a favourable application also in periodontal regeneration. Our results show that inflammation plays an important role in periodontal regeneration. PGE2 is a key mediator, which stimulates bone resorption also via a mechanism involving the inhibition of osteogenic differentiation of MSC as well as PDLSC. Therefore, regenerative approaches should always be conducted in combination with anti-inflammatory measures oriented to control inflammation.
