title: Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Pathway Is Induced by Mechanical Load and Reduces the Activity of Hedgehog Signaling in Chondrogenic Micromass Cell Cultures.
abstract: Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurohormone exerting protective function during various stress conditions either in mature or developing tissues. Previously we proved the presence of PACAP signaling elements in chicken limb bud-derived chondrogenic cells in micromass cell cultures. Since no data can be found if PACAP signaling is playing any role during mechanical stress in any tissues, we aimed to investigate its contribution in mechanotransduction during chondrogenesis. Expressions of the mRNAs of PACAP and its major receptor, PAC1 increased, while that of other receptors, VPAC1, VPAC2 decreased upon mechanical stimulus. Mechanical load enhanced the expression of collagen type X, a marker of hypertrophic differentiation of chondrocytes and PACAP addition attenuated this elevation. Moreover, exogenous PACAP also prevented the mechanical load evoked activation of hedgehog signaling: protein levels of Sonic and Indian Hedgehogs and Gli1 transcription factor were lowered while expressions of Gli2 and Gli3 were elevated by PACAP application during mechanical load. Our results suggest that mechanical load activates PACAP signaling and exogenous PACAP acts against the hypertrophy inducing effect of mechanical load.
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Medical and Health Science Centre, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. 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, Medical and Health Science Centre, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. valaki006@gmail.com.
authors.forename: Eszter
authors.initials: E
authors.lastname: Szentléleky
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Medical and Health Science Centre, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. somogyics@anat.med.unideb.hu.
authors.forename: Csilla Szűcs
authors.initials: CS
authors.lastname: Somogyi
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Medical and Health Science Centre, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. takacs.roland@med.unideb.hu.
authors.forename: Roland
authors.initials: R
authors.lastname: Takács
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Medical and Health Science Centre, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. luysica@gmail.com.
authors.forename: Nóra
authors.initials: N
authors.lastname: Dobrosi
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Medical and Health Science Centre, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. engler.mate.janos@med.unideb.hu.
authors.forename: Máté
authors.initials: M
authors.lastname: Engler
authors.affiliation: Department of Anatomy, MTA-PTE "Lendület" PACAP Research Team, University of Pécs, Medical School, Szigeti út 12, H-7624 Pécs, Hungary. andreatamassz@gmail.com.
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. dora.reglodi@aok.pte.hu.
authors.forename: Dóra
authors.initials: D
authors.lastname: Reglődi
authors.affiliation: Department of Anatomy, Histology and Embryology, University of Debrecen, Medical and Health Science Centre, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. roza@anat.med.unideb.hu.
authors.forename: Róza
authors.initials: R
authors.lastname: Zákány
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000235:genetics / Q000378:metabolism*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D015534:Trans-Activators / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: D053823:Hedgehog Proteins; D015513:Oncogene Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1
keywords: Indian hedgehog; Sonic hedgehog; chondrocyte differentiation; hypertrophy; mechanotransduction