Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signalling Enhances Osteogenesis in UMR-106 Cell Line
Autor: | Csilla Somogyi, Csaba Matta, Éva Bakó, Tibor Hajdú, Róza Zákány, Dóra Reglődi, Andrea Tamas, János Fodor, László Csernoch, Tamás Juhász, Éva Katona, Solveig Lind Helgadottir, Roland Ádám Takács, Gábor Tóth |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Patched Receptors
endocrine system medicine.medical_specialty Kruppel-Like Transcription Factors Adenylate kinase Core Binding Factor Alpha 1 Subunit Receptors Cell Surface Biology CREB Bone morphogenetic protein Zinc Finger Protein GLI1 Collagen Type I Smad1 Protein Cellular and Molecular Neuroscience Osteogenesis Cell Line Tumor Internal medicine medicine Animals Elméleti orvostudományok Cyclic AMP Response Element-Binding Protein Receptor Protein kinase A Transcription factor Cell Proliferation Osteoblast General Medicine Orvostudományok Alkaline Phosphatase Cyclic AMP-Dependent Protein Kinases Rats Cell biology RUNX2 Endocrinology medicine.anatomical_structure Bone Morphogenetic Proteins biology.protein Pituitary Adenylate Cyclase-Activating Polypeptide hormones hormone substitutes and hormone antagonists Receptors Pituitary Adenylate Cyclase-Activating Polypeptide Type I Signal Transduction Transcription Factors |
Popis: | Presence of the pituitary adenylate cyclase-activating polypeptide (PACAP) signalling has been proved in various peripheral tissues. PACAP can activate protein kinase A (PKA) signalling via binding to pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1), vasoactive intestinal polypeptide receptor (VPAC) 1 or VPAC2 receptor. Since little is known about the role of this regulatory mechanism in bone formation, we aimed to investigate the effect of PACAP on osteogenesis of UMR-106 cells. PACAP 1-38 as an agonist and PACAP 6-38 as an antagonist of PAC1 were added to the culture medium. Surprisingly, both substances enhanced protein expressions of collagen type I, osterix and alkaline phosphatase, along with higher cell proliferation rate and an augmented mineralisation. Although expression of PKA was elevated, no alterations were detected in the expression, phosphorylation and nuclear presence of CREB, but increased nuclear appearance of Runx2, the key transcription factor of osteoblast differentiation, was shown. Both PACAPs increased the expressions of bone morphogenetic proteins (BMPs) 2, 4, 6, 7 and Smad1 proteins, as well as that of Sonic hedgehog, PATCH1 and Gli1. Data of our experiments indicate that activation of PACAP pathway enhances bone formation of UMR-106 cells and PKA, BMP and Hedgehog signalling pathways became activated. We also found that PACAP 6-38 did not act as an antagonist of PACAP signalling in UMR-106 cells. |
Databáze: | OpenAIRE |
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