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

Christopher Fellows, Rebecca Williams, Iwan R. Davies, Kajal Gohil, Duncan M. Baird, John Fairclough, Paul Rooney, Charles Archer, Ilyas Khan Orcid Logo

Scientific Reports, Volume: 7, Issue: 1, Start page: 41421

Swansea University Authors: Christopher Fellows, Charles Archer, Ilyas Khan Orcid Logo

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DOI (Published version): 10.1038/srep41421

Abstract

In recent years it has become increasingly clear that articular cartilage harbours a viable pool ofprogenitor cells and interest has focussed on their role during development and disease. Analysis ofprogenitor numbers using fluorescence-activated sorting techniques has resulted in wide-rangingestima...

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Published in: Scientific Reports
ISSN: 2045-2322
Published: Springer Science and Business Media LLC 2017
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spelling 2020-07-31T14:31:10.9919346 v2 31768 2017-01-26 Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence f720be0016a59d4dab49bc956c1c242a Christopher Fellows Christopher Fellows true false d23ecc9643761bda7acd0f488ed0783e Charles Archer Charles Archer true false 2536d955ff70e7b77063a8efe9103161 0000-0002-3886-1987 Ilyas Khan Ilyas Khan true false 2017-01-26 FGMHL In recent years it has become increasingly clear that articular cartilage harbours a viable pool ofprogenitor cells and interest has focussed on their role during development and disease. Analysis ofprogenitor numbers using fluorescence-activated sorting techniques has resulted in wide-rangingestimates, which may be the result of context-dependent expression of cell surface markers. Wehave used a colony-forming assay to reliably determine chondroprogenitor numbers in normal andosteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P &#60; 0.0001). Intriguingly,cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilagerevealed the presence of a divergent progenitor subpopulation characterised by an early senescentphenotype. Divergent sub-populations displayed increased senescence-associated β–galactosidaseactivity, lower average telomere lengths but retained the capacity to undergo multi-lineagedifferentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be asignificant component of the pathological process. This study shows that although early senescenceis an inherent property of a subset of activated progenitors, there is also a pool of progenitors withextended viability and regenerative potential residing within osteoarthritic cartilage. Journal Article Scientific Reports 7 1 41421 Springer Science and Business Media LLC 2045-2322 2 2 2017 2017-02-02 10.1038/srep41421 COLLEGE NANME Medicine, Health and Life Science - Faculty COLLEGE CODE FGMHL Swansea University 2020-07-31T14:31:10.9919346 2017-01-26T11:51:49.5483918 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Christopher Fellows 1 Rebecca Williams 2 Iwan R. Davies 3 Kajal Gohil 4 Duncan M. Baird 5 John Fairclough 6 Paul Rooney 7 Charles Archer 8 Ilyas Khan 0000-0002-3886-1987 9 0031768-15022017131015.pdf srep41421.pdf 2017-02-15T13:10:15.2870000 Output 1478311 application/pdf Version of Record true 2017-02-02T00:00:00.0000000 This work is licensed under a Creative Commons Attribution 4.0 International License. true eng http://creativecommons.org/licenses/by/4.0/
title Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence
spellingShingle Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence
Christopher Fellows
Charles Archer
Ilyas Khan
title_short Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence
title_full Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence
title_fullStr Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence
title_full_unstemmed Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence
title_sort Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence
author_id_str_mv f720be0016a59d4dab49bc956c1c242a
d23ecc9643761bda7acd0f488ed0783e
2536d955ff70e7b77063a8efe9103161
author_id_fullname_str_mv f720be0016a59d4dab49bc956c1c242a_***_Christopher Fellows
d23ecc9643761bda7acd0f488ed0783e_***_Charles Archer
2536d955ff70e7b77063a8efe9103161_***_Ilyas Khan
author Christopher Fellows
Charles Archer
Ilyas Khan
author2 Christopher Fellows
Rebecca Williams
Iwan R. Davies
Kajal Gohil
Duncan M. Baird
John Fairclough
Paul Rooney
Charles Archer
Ilyas Khan
format Journal article
container_title Scientific Reports
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container_issue 1
container_start_page 41421
publishDate 2017
institution Swansea University
issn 2045-2322
doi_str_mv 10.1038/srep41421
publisher Springer Science and Business Media LLC
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title Faculty of Medicine, Health and Life Sciences
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hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description In recent years it has become increasingly clear that articular cartilage harbours a viable pool ofprogenitor cells and interest has focussed on their role during development and disease. Analysis ofprogenitor numbers using fluorescence-activated sorting techniques has resulted in wide-rangingestimates, which may be the result of context-dependent expression of cell surface markers. Wehave used a colony-forming assay to reliably determine chondroprogenitor numbers in normal andosteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P &#60; 0.0001). Intriguingly,cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilagerevealed the presence of a divergent progenitor subpopulation characterised by an early senescentphenotype. Divergent sub-populations displayed increased senescence-associated β–galactosidaseactivity, lower average telomere lengths but retained the capacity to undergo multi-lineagedifferentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be asignificant component of the pathological process. This study shows that although early senescenceis an inherent property of a subset of activated progenitors, there is also a pool of progenitors withextended viability and regenerative potential residing within osteoarthritic cartilage.
published_date 2017-02-02T03:38:48Z
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