title: Pregnancy-associated plasma protein-a is involved in matrix mineralization of human adult mesenchymal stem cells and angiogenesis in the chick chorioallontoic membrane.
abstract: Pregnancy-associated plasma protein A (PAPP-A) is an IGF binding protein 4 protease that can function to increase local IGF-I bioavailability. Aside from its assumed role during pregnancy, in vitro and in vivo studies have indicated roles for PAPP-A in IGF-I-mediated wound healing, vascular repair, and bone formation. Because bone morphogenetic protein 2 (BMP-2) is known to up-regulate Igf-I gene expression, we hypothesized that PAPP-A may be involved in BMP-2 mechanisms in bone formation. To test this hypothesis, we quantified gene expression of Papp-A in response to BMP-2 treatment and runt-related transcription factor 2, Osterix, and Igf-I in response to PAPP-A protein treatment in human adult mesenchymal stem cells. Our results demonstrate that BMP-2 directly up-regulated Papp-A gene and protein expression. Purified PAPP-A protein directly up-regulated runt-related transcription factor 2 and Igf-I gene expression but not Osterix. When added in combination with recombinant human BMP-2, PAPP-A increased matrix mineralization in the absence of dexamethasone. PAPP-A further demonstrated an angiogenic effect in the chick chorioallontoic membrane, which implicates a critical developmental role and possible therapeutic potential. Our findings suggest that PAPP-A functions in the formation of mineralized tissues through direct up-regulation of key genes. Furthermore, PAPP-A is involved in the formation of new blood vessels, which is essential for proper bone regeneration.
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, 5000 Forbes Avenue, 1201 Hamburg Hall, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Jadlowiec
authors.forename: Diana
authors.initials: D
authors.lastname: Dongell
authors.forename: Jason
authors.initials: J
authors.lastname: Smith
authors.forename: Cheryl
authors.initials: C
authors.lastname: Conover
authors.forename: Phil
authors.initials: P
authors.lastname: Campbell
mesh_terms: D000328:Adult; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply* / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011266:Pregnancy-Associated Plasma Protein-A / Q000494:pharmacology / Q000502:physiology*; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D007334:Insulin-Like Growth Factor I; D011266:Pregnancy-Associated Plasma Protein-A