Signalling Alterations in Bones of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Gene Deficient Mice

• Published in: International journal of molecular sciences Vol. 19; no. 9; p. 2538
• Main Authors: Józsa, Gergő, Szegeczki, Vince, Pálfi, Andrea, Kiss, Tamás, Helyes, Zsuzsanna, Fülöp, Balázs, Cserháti, Csaba, Daróczi, Lajos, Tamás, Andrea, Zákány, Róza, Reglődi, Dóra, Juhász, Tamás
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.08.2018; MDPI
• Subjects: Alkaline phosphatase; Alkaline Phosphatase - genetics; Alkaline Phosphatase - metabolism; alkaline phosphatase activity; Animals; Arthritis; Biocompatibility; Biomechanics; Biomedical materials; BMP; bone fragility; Bone growth; Bone matrix; Bone morphogenetic proteins; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - metabolism; Bones; Calcification; Calcium; Calcium - metabolism; Calcium ions; Cell Differentiation - genetics; Chondrogenesis; Chondrogenesis - genetics; Collagen; Collagen (type I); collagen expression; Collagen Type I - genetics; Collagen Type I - metabolism; Cortical bone; Differentiation (biology); Femur; Femur - diagnostic imaging; Femur - metabolism; Fragility; Gene Expression; hedgehog; Hedgehog protein; inorganic matrix; Kinases; Mechanical properties; Mice, Knockout; Morphology; Neuropeptides; Osteogenesis; Osteogenesis - genetics; Pituitary adenylate cyclase-activating polypeptide; Pituitary Adenylate Cyclase-Activating Polypeptide - deficiency; Pituitary Adenylate Cyclase-Activating Polypeptide - genetics; Polypeptides; Proteins; Rodents; Signal Transduction - genetics; Stem cells; Transcription factors; X-Ray Microtomography; Hungary; inorganic matrix; alkaline phosphatase activity; BMP; hedgehog; bone fragility; collagen expression
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19092538

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 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 Ca 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 bone formation.