Signalling alterations in bones of pituitary adenylate cyclase activating polypeptide (PACAP) gene deficient mice

Gergő Józsa, Vince Szegeczki, Andrea Pálfi, Tamás Kiss, Zsuzsanna Helyes, Balázs Fülöp, Csaba Cserháti, Lajos Daróczi, Andrea Tamás, Róza Zákány, Dóra Reglődi, Tamás Juhász

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with diverse developmental roles, including differentiation of skeletal elements. It is a positive regulatory factor of chondrogenesis and osteogenic differentiation in vitro, but little is known about its in vivo role in bone formation. In our experiments, diaphyses of long bones from hind limbs of PACAP gene-deficient mice showed changes in thickness and increased staining intensity. Our main goal was to perform a detailed morphological and molecular biological analysis of femurs from PACAP knockout (KO) and wild type (WT) mice. Transverse diameter and anterior cortical bone thickness of KO femurs showed significant alterations with disturbed Ca2+ accumulation and collagen type I expression. Higher expression and activity of alkaline phosphatase were also observed, accompanied by increased fragility PACAP KO femurs. Increased expression of the elements of bone morphogenic protein (BMP) and hedgehog signalling was also observed, and are possibly responsible for the compensation mechanism accounting for the slight morphological changes. In summary, our results show that lack of PACAP influences molecular and biomechanical properties of bone matrix, activating various signalling cascade changes in a compensatory fashion. The increased fragility of PACAP KO femur further supports the role of endogenous PACAP in in vivo bone formation.

Original languageEnglish
Article number2538
JournalInternational journal of molecular sciences
Volume19
Issue number9
DOIs
Publication statusPublished - Sep 2018

Keywords

  • Alkaline phosphatase activity
  • BMP
  • Bone fragility
  • Collagen expression
  • Hedgehog
  • Inorganic matrix

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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