Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signalling Enhances Osteogenesis in UMR-106 Cell Line

Tamás Juhász, Csaba Matta, Éva Katona, Csilla Somogyi, Roland Takács, Tibor Hajdú, Solveig Lind Helgadottir, János Fodor, László Csernoch, Gábor Tóth, Éva Bakó, Dóra Reglődi, Andrea Tamás, Róza Zákány

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)555-573
Number of pages19
JournalJournal of Molecular Neuroscience
Volume54
Issue number3
DOIs
Publication statusPublished - Jan 1 2014

Keywords

  • CREB
  • Cellular proliferation
  • Mineralisation
  • PACAP 6-38
  • PKA
  • Sonic hedgehog

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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  • Cite this

    Juhász, T., Matta, C., Katona, É., Somogyi, C., Takács, R., Hajdú, T., Helgadottir, S. L., Fodor, J., Csernoch, L., Tóth, G., Bakó, É., Reglődi, D., Tamás, A., & Zákány, R. (2014). Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signalling Enhances Osteogenesis in UMR-106 Cell Line. Journal of Molecular Neuroscience, 54(3), 555-573. https://doi.org/10.1007/s12031-014-0389-1