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. ORCID: https://orcid.org/0000-0001-8408-5467, 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:	08 May 2023 19:16
URI:	https://orca.cardiff.ac.uk/id/eprint/98192

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