title: Nanotopographical induction of osteogenesis through adhesion, bone morphogenic protein cosignaling, and regulation of microRNAs.
abstract: It is emerging that nanotopographical information can be used to induce osteogenesis from mesenchymal stromal cells from the bone marrow, and it is hoped that this nanoscale bioactivity can be utilized to engineer next generation implants. However, the osteogenic mechanism of surfaces is currently poorly understood. In this report, we investigate mechanism and implicate bone morphogenic protein (BMP) in up-regulation of RUNX2 and show that RUNX2 and its regulatory miRNAs are BMP sensitive. Our data demonstrate that osteogenic nanotopography promotes colocalization of integrins and BMP2 receptors in order to enhance osteogenic activity and that vitronectin is important in this interface. This provides insight that topographical regulation of adhesion can have effects on signaling cascades outside of cytoskeletal signaling and that adhesions can have roles in augmenting BMP signaling.
authors.affiliation: Centre for Cell Engineering, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Joseph Black Building, University of Glasgow , Glasgow, G12 8QQ, U.K.
authors.forename: Jingli
authors.initials: J
authors.lastname: Yang
authors.forename: Laura E
authors.initials: LE
authors.lastname: McNamara
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Gadegaard
authors.forename: Enateri V
authors.initials: EV
authors.lastname: Alakpa
authors.forename: Karl V
authors.initials: KV
authors.lastname: Burgess
authors.forename: R M Dominic
authors.initials: RM
authors.lastname: Meek
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Dalby
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D036103:Nanotechnology; D010012:Osteogenesis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D019485:Bone Morphogenetic Proteins; D035683:MicroRNAs
keywords: BMP and integrin signaling; mesenchymal stem cells; metabolomics; nanotopography; osteogenesis