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

Gergő Józsa, Vince Szegeczki, Andrea Pálfi, Tamás Kiss, Z. Helyes, Balázs Fülöp, C. Cserháti, L. Daróczi, A. Tamás, Róza Zákány, D. Reglodi, Tamás Juhász

Research output: Contribution to journalArticle

2 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 1 2018

Fingerprint

Pituitary Adenylate Cyclase-Activating Polypeptide
polypeptides
genes
bones
mice
Bone
Genes
femur
Bone and Bones
Femur
osteogenesis
Osteogenesis
Hedgehog Proteins
Chondrogenesis
Diaphyses
bioassay
Bone Matrix
phosphatases
molecular properties
Phosphatases

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

Cite this

Signalling alterations in bones of pituitary adenylate cyclase activating polypeptide (PACAP) gene deficient mice. / Józsa, Gergő; Szegeczki, Vince; Pálfi, Andrea; Kiss, Tamás; Helyes, Z.; Fülöp, Balázs; Cserháti, C.; Daróczi, L.; Tamás, A.; Zákány, Róza; Reglodi, D.; Juhász, Tamás.

In: International Journal of Molecular Sciences, Vol. 19, No. 9, 2538, 01.09.2018.

Research output: Contribution to journalArticle

Józsa, Gergő ; Szegeczki, Vince ; Pálfi, Andrea ; Kiss, Tamás ; Helyes, Z. ; Fülöp, Balázs ; Cserháti, C. ; Daróczi, L. ; Tamás, A. ; Zákány, Róza ; Reglodi, D. ; Juhász, Tamás. / Signalling alterations in bones of pituitary adenylate cyclase activating polypeptide (PACAP) gene deficient mice. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 9.
@article{15298edae0634b8db989e755ebd2efa5,
title = "Signalling alterations in bones of pituitary adenylate cyclase activating polypeptide (PACAP) gene deficient mice",
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.",
keywords = "Alkaline phosphatase activity, BMP, Bone fragility, Collagen expression, Hedgehog, Inorganic matrix",
author = "Gergő J{\'o}zsa and Vince Szegeczki and Andrea P{\'a}lfi and Tam{\'a}s Kiss and Z. Helyes and Bal{\'a}zs F{\"u}l{\"o}p and C. Cserh{\'a}ti and L. Dar{\'o}czi and A. Tam{\'a}s and R{\'o}za Z{\'a}k{\'a}ny and D. Reglodi and Tam{\'a}s Juh{\'a}sz",
year = "2018",
month = "9",
day = "1",
doi = "10.3390/ijms19092538",
language = "English",
volume = "19",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",

}

TY - JOUR

T1 - Signalling alterations in bones of pituitary adenylate cyclase activating polypeptide (PACAP) gene deficient mice

AU - Józsa, Gergő

AU - Szegeczki, Vince

AU - Pálfi, Andrea

AU - Kiss, Tamás

AU - Helyes, Z.

AU - Fülöp, Balázs

AU - Cserháti, C.

AU - Daróczi, L.

AU - Tamás, A.

AU - Zákány, Róza

AU - Reglodi, D.

AU - Juhász, Tamás

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

KW - Alkaline phosphatase activity

KW - BMP

KW - Bone fragility

KW - Collagen expression

KW - Hedgehog

KW - Inorganic matrix

UR - http://www.scopus.com/inward/record.url?scp=85052494285&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052494285&partnerID=8YFLogxK

U2 - 10.3390/ijms19092538

DO - 10.3390/ijms19092538

M3 - Article

C2 - 30150589

AN - SCOPUS:85052494285

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 9

M1 - 2538

ER -