Abnormally short telomeres in knee tissue linked to
23 January 2012
Cells from osteoarthritic knees have abnormally shortened
telomeres — the section of DNA on the end of chromosomes that shortens
with age. In addition, the percentage of cells with ultra short
telomeres increases the closer to the damaged region within the knee
joint. The research is published in BioMed Central's open access journal
Arthritis Research & Therapy .
When a cell divides it first duplicates its DNA and, because the DNA
replication machinery fails to get all the way to the end, with each
successive cell division a little bit more is missed. Therefore the
very ends of chromosomes, called telomeres, become shorter as we
While the shortening of telomeres is an unavoidable
side effect of getting older, telomeres can also shorten as a result
of sudden cell damage, including oxidative damage. Abnormally short
telomeres have been found in some types of cancer, possibly because
of the rapid cell division the cells are forced to undergo.
There has been some evidence from preliminary work done on cultured
cells that the average telomere length is also reduced in
osteoarthritis (OA). A team of researchers from Denmark used newly
developed technology (called universal single telomere length assay)
to look in detail at the telomeres of cells taken from the knees of
people who had undergone joint replacement surgery. Their results
showed that average telomere length was, as expected, shortened in
OA, but that also 'ultra short' telomeres, thought to be due to
oxidative stress, were even more strongly associated with OA.
Maria Harbo who led this research explained, "We see both a
reduced mean telomere length and an increase in the number of cells
with ultra short telomeres associated with increased severity of OA,
proximity to the most damaged section of the joint, and with
senescence. Senescence can be most simply explained as biological
aging and senescent cartilage within joints is unable to repair
She continued, "The telomere story
shows us that there are, in theory, two processes going on in OA.
Age-related shortening of telomeres, which leads to the inability of
cells to continue dividing and so to cell senescence, and ultra
short telomeres, probably caused by compression stress during use,
which lead to senescence and failure of the joint to repair itself.
We believe the second situation to be the most important in OA. The
damaged cartilage could add to the mechanical stress within the
joint and so cause a feedback cycle driving the progression of the
1. Maria Harbo et al. The distribution pattern of
critically short telomeres in human osteoarthritic knees.
Arthritis Research & Therapy 2012 (in press). Provisional