title: BMP-2 induces versican and hyaluronan that contribute to post-EMT AV cushion cell migration.
abstract: Distal outgrowth and maturation of mesenchymalized endocardial cushions are critical morphogenetic events during post-EMT atrioventricular (AV) valvuloseptal morphogenesis. We explored the role of BMP-2 in the regulation of valvulogenic extracellular matrix (ECM) components, versican and hyaluronan (HA), and cell migration during post-EMT AV cushion distal outgrowth/expansion. We observed intense staining of versican and HA in AV cushion mesenchyme from the early cushion expansion stage, Hamburger and Hamilton (HH) stage-17 to the cushion maturation stage, HH stage-29 in the chick. Based on this expression pattern we examined the role of BMP-2 in regulating versican and HA using 3D AV cushion mesenchymal cell (CMC) aggregate cultures on hydrated collagen gels. BMP-2 induced versican expression and HA deposition as well as mRNA expression of versican and Has2 by CMCs in a dose dependent manner. Noggin, an antagonist of BMP, abolished BMP-2-induced versican and HA as well as mRNA expression of versican and Has2. We further examined whether BMP-2-promoted cell migration was associated with expression of versican and HA. BMP-2- promoted cell migration was significantly impaired by treatments with versican siRNA and HA oligomer. In conclusion, we provide evidence that BMP-2 induces expression of versican and HA by AV CMCs and that these ECM components contribute to BMP-2-induced CMC migration, indicating critical roles for BMP-2 in distal outgrowth/expansion of mesenchymalized AV cushions.
authors.affiliation: Department of Regenerative Medicine and Cell Biology and Cardiovascular Developmental Biology Center, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Kei
authors.initials: K
authors.lastname: Inai
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Burnside
authors.forename: Stanley
authors.initials: S
authors.lastname: Hoffman
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Toole
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sugi
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002642:Chick Embryo; D054089:Endocardial Cushions / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D053675:Versicans / Q000235:genetics / Q000378:metabolism*
chemical_list: D055396:Bone Morphogenetic Protein 2; D012333:RNA, Messenger; D053675:Versicans; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase