Pieles, Oliver and Reichert, Torsten E. and Morsczeck, Christian (2022) Protein kinase A is activated during bone morphogenetic protein 2-induced osteogenic differentiation of dental follicle stem cells via endogenous parathyroid hormone-related protein. ARCHIVES OF ORAL BIOLOGY, 138: 105409. ISSN 0003-9969, 1879-1506
Full text not available from this repository. (Request a copy)Abstract
Objective: The aim of this study was to investigate the mechanisms of how protein kinase A (PKA) is activated during bone morphogenetic protein 2 (BMP2)-induced osteogenic differentiation in dental follicle stem cells. Design: Human dental follicle stem cells were cultured and treated with a BMP2-containing osteogenic differentiation medium or differentiation medium without BMP2. Specific siRNAs and substances/proteins were used to modulate pathways. PKA activity and activity of alkaline phosphatase were determined. Expression of targets was measured by Western Blots and reverse transcription-quantitative polymerase chain reaction, while protein interactions were investigated by immunoprecipitation. Immunofluorescence staining was used for subcellular target localization. Results: PKA activity is stimulated after osteogenic induction by BMP2. Differentiation medium without BMP2 strongly induces BMP2 gene expression, which correlates with downstream target expression. Elevation of cAMP levels does not affect alkaline phosphatase activity and PKA does not directly interact with Smad 4. However, PKA activation requires expression of parathyroid hormone-related protein (PTHrP), which is stimulated after BMP2-induced differentiation. Furthermore, neither supplementation with PTHrP nor with the receptor antagonist parathyroid hormone (7-34) affects PKA activity. Thus, endogenous PTHrP expression is required for PKA activation and immunofluorescence staining shows that PTHrP is mainly located in the nucleus of dental follicle stem cells. Beyond, knockdown of PKA stimulates the BMP2 signaling pathway and down-stream expression of PTHrP. Conclusions: BMP2-induced osteogenic differentiation activates PKA in dental follicle stem cells via endogenous expression of PTHrP. Additionally, PKA inhibits BMP2 signaling and expression of PTHrP in a negative feedback loop.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OSTEOBLAST DIFFERENTIATION; SIGNALING PATHWAY; EXPRESSION; PEPTIDE; GENE; REGENERATION; RECEPTORS; SUBUNITS; SUSTAINS; PTHRP; Dental follicle stem cells; Osteogenic Differentiation; Protein kinase A; Bone morphogenetic protein 2; Parathyroid hormone-related protein |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Jan 2024 10:36 |
| Last Modified: | 09 Jan 2024 10:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57121 |
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