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

Sci Rep. 2017 Feb 2:7:41421. doi: 10.1038/srep41421.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Adult Stem Cells / pathology
  • Aged
  • Aged, 80 and over
  • Bromodeoxyuridine / metabolism
  • Cartilage, Articular / pathology*
  • Cell Nucleus / metabolism
  • Cell Separation
  • Cellular Senescence*
  • Chromosomes, Human / metabolism
  • Clone Cells
  • Humans
  • Linear Models
  • Middle Aged
  • Osteoarthritis / pathology*
  • Stem Cells / pathology*
  • Telomere / metabolism*
  • beta-Galactosidase / metabolism

Substances

  • beta-Galactosidase
  • Bromodeoxyuridine