Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence.
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 senescence-associated 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.
Cardiff University, School of Biosciences, Cardiff, UK.|Centre for NanoHealth, Swansea University Medical School, Swansea, UK.|University of Surrey, Department of Veterinary Preclinincal Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, Guildford, UK.
Christopher R
CR
Fellows
Cardiff University, School of Biosciences, Cardiff, UK.
Rebecca
R
Williams
Cardiff University, School of Biosciences, Cardiff, UK.
Iwan R
IR
Davies
Cardiff University, School of Biosciences, Cardiff, UK.
Kajal
K
Gohil
Cardiff University, Institute of Cancer and Genetics, Cardiff, UK.
Duncan M
DM
Baird
University Hospital of Wales, Cardiff, UK.
John
J
Fairclough
NHS Blood and Transplant Tissue Services, Liverpool, UK.
Paul
P
Rooney
Centre for NanoHealth, Swansea University Medical School, Swansea, UK.
Charles W
CW
Archer
Centre for NanoHealth, Swansea University Medical School, Swansea, UK.
Ilyas M
IM
Khan
D000328:Adult; D053687:Adult Stem Cells / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001973:Bromodeoxyuridine / Q000378:metabolism; D002358:Cartilage, Articular / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D016922:Cellular Senescence; D002877:Chromosomes, Human / Q000378:metabolism; D002999:Clone Cells; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D010003:Osteoarthritis / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*; D016615:Telomere / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D001616:beta-Galactosidase; D001973:Bromodeoxyuridine