title: Nanotopology potentiates growth hormone signalling and osteogenesis  of mesenchymal stem cells.
abstract: Custom engineered materials can influence the differentiation of human mesenchymal stem cells (MSCs) towards osteoblasts, chondrocytes and adipocytes, through the control of chemistry, stiffness and nanoscale topography. Here we demonstrate that polycaprolactone growth surfaces engineered with disordered (but controlled) 120 nm diameter dots (NSQ50), but not flat surfaces, promote osteogenic conversion of MSCs in the absence of other osteogenic stimuli. Differentiating MSCs on NSQ50 were found to express growth hormone receptors (GH) and stimulation with recombinant human GH (rhGH) further enhanced NSQ50-driven osteogenic conversion of MSCs. This increased osteogenesis coincided with an enhanced ability of GH to activate ERK MAP kinase on NSQ50, but not on flat topology. The importance of ERK for MSC differentiation was demonstrated by using the inhibitor of ERK activation, U0126, which completely suppressed osteogenesis of GH-stimulated MSCs on NSQ50. The ability of GH to activate ERK in MSCs may therefore be a central control mechanism underlying bone development and growth.
authors.forename: Jessie R
authors.initials: JR
authors.lastname: Wang
authors.forename: S Faisal
authors.initials: SF
authors.lastname: Ahmed
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Gadegaard
authors.forename: R M Dominic
authors.initials: RM
authors.lastname: Meek
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Dalby
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Yarwood
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D036103:Nanotechnology; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology*; D011091:Polyesters / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D011091:Polyesters; D012333:RNA, Messenger; D019382:Human Growth Hormone; C016240:polycaprolactone; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase