2134/24585 Neil Martin Neil Martin Kathryn Aguilar-Agon Kathryn Aguilar-Agon G.P. Robinson G.P. Robinson Darren Player Darren Player Mark Turner Mark Turner S.D. Myers S.D. Myers Mark Lewis Mark Lewis Hypoxia impairs muscle function and reduces myotube size in tissue engineered skeletal muscle Loughborough University 2017 untagged Medical and Health Sciences not elsewhere classified 2017-03-30 15:06:05 Journal contribution https://repository.lboro.ac.uk/articles/journal_contribution/Hypoxia_impairs_muscle_function_and_reduces_myotube_size_in_tissue_engineered_skeletal_muscle/9620588 Contemporary tissue engineered skeletal muscle models display a high degree of physiological accuracy compared with native tissue, and therefore may be excellent platforms to understand how various pathologies affect skeletal muscle. Chronic obstructive pulmonary disease (COPD) is a lung disease which causes tissue hypoxia and is characterised by muscle fibre atrophy and impaired muscle function. In the present study we exposed engineered skeletal muscle to varying levels of oxygen (O2; 21-1%) for 24 hours in order to see if a COPD like muscle phenotype could be recreated in vitro, and if so, at what degree of hypoxia this occured. Maximal contractile force was attenuated in hypoxia compared to 21% O2; with culture at 5 and 1% O2 causing the most pronounced effects with 62 and 56% decrements in force respectively. Furthermore at these levels of O2, myotubes within the engineered muscles displayed significant atrophy which was not seen at higher O2 levels. At the molecular level we observed increases in mRNA expression of MuRF-1 only at 1% O2 whereas MAFbx expression was elevated at 10, 5 and 1% O2. In addition, p70S6 kinase phosphorylation (a downstream effector of mTORC1) was reduced when engineered muscle was cultured at 1%, with no significant changes seen above this O2 level. Overall, these data suggest that engineered muscle exposed to O2 levels of ≤5% adapts in a manner similar to that seen in COPD patients, and thus may provide a novel model for further understanding muscle wasting associated with tissue hypoxia.