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Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence

Fellows, Christopher R., Williams, Rebecca, Davies, Iwan R,, Gohil, Kajal, Baird, Duncan M., Fairclough, John, Rooney, Paul, Archer, Charles W. and Khan, Ilyas M. 2017. Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence. Scientific Reports 7 , 41421. 10.1038/srep41421

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Abstract

In recent years it has become increasingly clear that articular cartilage harbours a viable pool of progenitor cells and interest has focussed on their role during development and disease. Analysis of progenitor numbers using fluorescence-activated sorting techniques has resulted in wide-ranging estimates, which may be the result of context-dependent expression of cell surface markers. We have used a colony-forming assay to reliably determine chondroprogenitor numbers in normal and osteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P < 0.0001). Intriguingly, cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilage revealed the presence of a divergent progenitor subpopulation characterised by an early senescent phenotype. Divergent sub-populations displayed increased senescenceassociated β–galactosidase activity, lower average telomere lengths but retained the capacity to undergo multi-lineage differentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be a significant component of the pathological process. This study shows that although early senescence is an inherent property of a subset of activated progenitors, there is also a pool of progenitors with extended viability and regenerative potential residing within osteoarthritic cartilage.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Biosciences
Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Nature Publishing Group
Date of First Compliant Deposit: 10 February 2017
Date of Acceptance: 19 December 2016
Last Modified: 25 Oct 2019 22:20
URI: http://orca-mwe.cf.ac.uk/id/eprint/98192

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