Protein kinase A is activated during bone morphogenetic protein 2-induced osteogenic differentiation of dental follicle stem cells via endogenous parathyroid hormone-related protein

Pieles, Oliver; Reichert, Torsten E.; Morsczeck, Christian

doi:10.1016/j.archoralbio.2022.105409

Cited by 2 publications

(3 citation statements)

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“…These results suggest that inhibitory molecules of the canonical WNT pathway support both β-catenin and—at least under certain circumstances—the osteogenic differentiation in DFCs. Interestingly, β-catenin is also activated by protein kinase A (PKA), which itself is induced by BMP2 [ 49 , 61 ]. Activation of PKA supports osteogenic differentiation not only via activation of β-catenin and downstream induction of DLX3 expression but also through “off state” of the hedgehog signaling pathway, which can control osteogenic differentiation of DFCs [ 50 ].…”

Section: Molecular Mechanisms Of the Osteogenic Differentiation Of Dfcsmentioning

confidence: 99%

“…While activation of PKA/β-catenin by BMP2 is still not fully understood, recent work suggests that PKA in DFCs is activated via nuclear-localized PTHrP, which is also induced by BMP2. In contrast, PKA inhibits BMP2 signaling and expression of PTHrP in a negative feedback loop and controls the BMP2/DLX3 pathway [ 61 ].…”

Section: Molecular Mechanisms Of the Osteogenic Differentiation Of Dfcsmentioning

confidence: 99%

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Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells

Morsczeck

2022

IJMS

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Human dental follicle cells (DFCs) as periodontal progenitor cells are used for studies and research in regenerative medicine and not only in dentistry. Even if innovative regenerative therapies in medicine are often considered the main research area for dental stem cells, these cells are also very useful in basic research and here, for example, for the elucidation of molecular processes in the differentiation into mineralizing cells. This article summarizes the molecular mechanisms driving osteogenic differentiation of DFCs. The positive feedback loop of bone morphogenetic protein (BMP) 2 and homeobox protein DLX3 and a signaling pathway associated with protein kinase B (AKT) and protein kinase C (PKC) are presented and further insights related to other signaling pathways such as the WNT signaling pathway are explained. Subsequently, some works are presented that have investigated epigenetic modifications and non-coding ncRNAs and their connection with the osteogenic differentiation of DFCs. In addition, studies are presented that have shown the influence of extracellular matrix molecules or fundamental biological processes such as cellular senescence on osteogenic differentiation. The putative role of factors associated with inflammatory processes, such as interleukin 8, in osteogenic differentiation is also briefly discussed. This article summarizes the most important insights into the mechanisms of osteogenic differentiation in DFCs and is intended to be a small help in the direction of new research projects in this area.

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Section: Molecular Mechanisms Of the Osteogenic Differentiation Of Dfcsmentioning

confidence: 99%

Section: Molecular Mechanisms Of the Osteogenic Differentiation Of Dfcsmentioning

confidence: 99%

Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells

Morsczeck

2022

IJMS

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“…In human mesenchymal stem cells (MSCs), the addition of PTHrP could increase bone formation and decrease bone resorption ( 7 ). Bone morphogenetic protein 2 (BMP2) facilitated osteogenic differen-tiation in dental follicle stem cells via endogenous expression of PTHrP ( 8 ). Moreover, repression of PTHrP expression in neural stem cells (NSCs) inhibited prolifera-tion and differentiation and promoted apoptosis ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Parathyroid Hormone-Related Protein Promotes the Proliferation of Patient-Derived Glioblastoma Stem Cells via Activating cAMP/PKA Signaling Pathway

et al. 2023

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Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

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Protein kinase A is activated during bone morphogenetic protein 2-induced osteogenic differentiation of dental follicle stem cells via endogenous parathyroid hormone-related protein

Cited by 2 publications

References 36 publications

Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells

Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells

Parathyroid Hormone-Related Protein Promotes the Proliferation of Patient-Derived Glioblastoma Stem Cells via Activating cAMP/PKA Signaling Pathway

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