title: PACAP and VIP signaling in chondrogenesis and osteogenesis.
abstract: Skeletal development is a complex process regulated by multifactorial signaling cascades that govern proper tissue specific cell differentiation and matrix production. The influence of certain regulatory peptides on cartilage or bone development can be predicted but are not widely studied. In this review, we aimed to assemble and overview those signaling pathways which are modulated by PACAP and VIP neuropeptides and are involved in cartilage and bone formation. We discuss recent experimental data suggesting broad spectrum functions of these neuropeptides in osteogenic and chondrogenic differentiation, including the canonical downstream targets of PACAP and VIP receptors, PKA or MAPK pathways, which are key regulators of chondro- and osteogenesis. Recent experimental data support the hypothesis that PACAP is a positive regulator of chondrogenesis, while VIP has been reported playing an important role in the inflammatory reactions of surrounding joint tissues. Regulatory function of PACAP and VIP in bone development has also been proved, although the source of the peptides is not obvious. Crosstalk and collateral connections of the discussed signaling mechanisms make the system complicated and may obscure the pure effects of VIP and PACAP. Chondro-protective properties of PACAP during oxidative stress observed in our experiments indicate a possible therapeutic application of this neuropeptide.
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Faculty of Medicine, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. Electronic address: juhaszt@anat.med.unideb.hu.
authors.forename: Tamás
authors.initials: T
authors.lastname: Juhász
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Faculty of Medicine, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
authors.forename: Solveig Lind
authors.initials: SL
authors.lastname: Helgadottir
authors.affiliation: Department of Anatomy MTA-PTE "Lendület" PACAP Research Team, University of Pécs, Medical School, Szigeti út 12, H-7624 Pécs, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tamás
authors.affiliation: Department of Anatomy MTA-PTE "Lendület" PACAP Research Team, University of Pécs, Medical School, Szigeti út 12, H-7624 Pécs, Hungary.
authors.forename: Dóra
authors.initials: D
authors.lastname: Reglődi
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Faculty of Medicine, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
authors.forename: Róza
authors.initials: R
authors.lastname: Zákány
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide
keywords: BMP; CREB; Hedgehog; PKA; Runx2