A systems biology approach to defining regulatory mechanisms for cartilage and tendon cell phenotypes.
Phenotypic plasticity of adult somatic cells has provided emerging avenues for the development of regenerative therapeutics. In musculoskeletal biology the mechanistic regulatory networks of genes governing the phenotypic plasticity of cartilage and tendon cells has not been considered systematically. Additionally, a lack of strategies to effectively reproduce in vitro functional models of cartilage and tendon is retarding progress in this field. De- and redifferentiation represent phenotypic transitions that may contribute to loss of function in ageing musculoskeletal tissues. Applying a systems biology network analysis approach to global gene expression profiles derived from common in vitro culture systems (monolayer and three-dimensional cultures) this study demonstrates common regulatory mechanisms governing de- and redifferentiation transitions in cartilage and tendon cells. Furthermore, evidence of convergence of gene expression profiles during monolayer expansion of cartilage and tendon cells, and the expression of key developmental markers, challenges the physiological relevance of this culture system. The study also suggests that oxidative stress and PI3K signalling pathways are key modulators of in vitro phenotypes for cells of musculoskeletal origin.
Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health &Life Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, United Kingdom.
A J
AJ
Mueller
Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health &Life Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, United Kingdom.|The MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA).
S R
SR
Tew
Institute of Integrative Biology, Biosciences Building, University of Liverpool, Crown St., Liverpool, L69 7ZB, United Kingdom.
O
O
Vasieva
Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health &Life Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, United Kingdom.|The MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA).
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PD
Clegg
Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health &Life Sciences, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, United Kingdom.|The MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA).
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Canty-Laird
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