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
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