Pieles, Oliver and Reichert, Torsten E. and Morsczeck, Christian (2021) Classical isoforms of protein kinase C (PKC) and Akt regulate the osteogenic differentiation of human dental follicle cells via both beta-catenin and NF-kappa B. STEM CELL RESEARCH & THERAPY, 12 (1): 242. ISSN , 1757-6512
Full text not available from this repository. (Request a copy)Abstract
BackgroundHuman dental follicle cells (DFCs) are the precursor cells of the periodontium with a high potential for regenerative therapies of (alveolar) bone. However, the molecular mechanisms of osteogenic differentiation are inadequately understood. Classical isoforms of protein kinase C (PKC) are reported to inhibit osteogenesis of stem/precursor cells. This study evaluated the role of classical PKCs and potential downstream targets on the osteogenic differentiation of DFCs.MethodsDFCs were osteogenic differentiated with dexamethasone or bone morphogenetic protein 2 (BMP2). Expression of PKC and potential upstream/downstream regulators was manipulated using activators, inhibitors, and small interfering ribonucleic acid (siRNA). Expression of proteins was examined by Western blot analysis, while the activation levels of enzymes and transcription factors were examined by their phosphorylation states or by specific activation assays. Expression levels of osteogenic markers were examined by RT-qPCR (reverse transcription-quantitative polymerase chain reaction) analysis. Activity of alkaline phosphatase (ALP) and accumulation of calcium nodules by Alizarin Red staining were measured as indicators of mineralization.ResultsClassical PKCs like PKC alpha inhibit the osteogenic differentiation of DFCs, but do not interfere with the induction of differentiation. Inhibition of classical PKCs by Go6976 enhanced activity of Akt after osteogenic induction. Akt was also regulated during differentiation and especially disturbed BMP2-induced mineralization. The PKC/Akt axis was further shown to regulate the canonical Wnt signaling pathway and eventually nuclear expression of active beta -catenin during dexamethasone-induced osteogenesis. Moreover, the nuclear factor "kappa-light-chain-enhancer" of activated B cells (NF-kappa B) pathway is regulated during osteogenic differentiation of DFCs and via the PKC/Akt axis and disturbs the mineralization. Upstream, parathyroid hormone-related protein (PTHrP) sustained the activity of PKC, while Wnt5a inhibited it.ConclusionsOur results demonstrate that classical PKCs like PKC alpha and Akt regulate the osteogenic differentiation of DFCs partly via both beta -catenin and NF-kappa B.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; Dental follicle cells; Osteogenic differentiation; Mineralization; Protein kinase C; Akt; NF-kappa B; Canonical Wnt signaling; beta-catenin |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Aug 2022 06:05 |
| Last Modified: | 24 Aug 2022 06:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46362 |
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