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 systematicall...

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Bibliographic Details
Published in:Scientific reports 2016-09, Vol.6 (1), p.33956-33956, Article 33956
Main Authors: Mueller, A. J., Tew, S. R., Vasieva, O., Clegg, P. D., Canty-Laird, E. G.
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
631/114/2407
631/1647/2017/2079
631/553/1833
692/699/1670/1669
Biology
Cartilage
Cell culture
Drug development
Gene expression
Humanities and Social Sciences
multidisciplinary
Oxidative stress
Phenotypic plasticity
Plasticity
Science
Science (multidisciplinary)
Signal transduction
Somatic cells
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep33956