title: Acute mechanical overload increases IGF-I and MMP-9 mRNA in 3D tissue-engineered skeletal muscle.
abstract: Skeletal muscle (SkM) is a tissue that responds to mechanical load following both physiological (exercise) or pathophysiological (bed rest) conditions. The heterogeneity of human samples and the experimental and ethical limitations of animal studies provide a rationale for the study of SkM plasticity in vitro. Many current in vitro approaches of mechanical loading of SkM disregard the three-dimensional (3D) structure in vivo. Tissue engineered 3D SkM, that displays highly aligned and differentiated myotubes, was used to investigate mechano-regulated gene transcription of genes implicated in hypertrophy/atrophy. Static loading (STL) and ramp loading (RPL) at 10 % strain for 60 min were used as mechano-stimulation with constructs sampled immediately for RNA extraction. STL increased IGF-I mRNA compared to both RPL and CON (control, p = 0.003 and 0.011 respectively) whilst MMP-9 mRNA increased in STL and RPL compared to CON (both p < 0.05). IGFBP-2 mRNA was differentially regulated in RPL and STL compared to CON (p = 0.057), whilst a reduction in IGFBP-5 mRNA was found for STL and RPL compared to CON (both p < 0.05). There was no effect in the expression of putative atrophic genes, myostatin, MuRF-1 and MAFBx (all p > 0.05). These data demonstrate a transcriptional signature associated with SkM hypertrophy within a tissue-engineered model that more greatly recapitulates the in vivo SkM structure compared previously published studies.
authors.affiliation: Musculoskeletal Biology Research Group, School of Sport, Exercise and Health Sciences, Loughborough University, Leicestershire, LE11 3TU, UK, d.player@lboro.ac.uk.
authors.forename: D J
authors.initials: DJ
authors.lastname: Player
authors.forename: N R W
authors.initials: NR
authors.lastname: Martin
authors.forename: S L
authors.initials: SL
authors.lastname: Passey
authors.forename: A P
authors.initials: AP
authors.lastname: Sharples
authors.forename: V
authors.initials: V
authors.lastname: Mudera
authors.forename: M P
authors.initials: MP
authors.lastname: Lewis
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology*; D002460:Cell Line; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*; D032446:Myoblasts; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013314:Stress, Mechanical; D023822:Tissue Engineering
chemical_list: D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D020780:Matrix Metalloproteinase 9