11.
The importance of ultra-short telomeres in the development of human
hip osteoarthritis (OA)
Maria Harbo, Jean-Marie Delaisse, Per Kjærsgaard-Andersen, Flemming
Brandt Sørensen, Steen Kølvraa, Laila Bendix
Department of Clinical Genetics Vejle/Lillebaelt Hospital; Department of
Clinical Cell Biology, Vejle/Lillebaelt Hospital; Department of Orthopedic
Surgery, Vejle/Lillebaelt Hospital; Department of Clinical Pathology,
Vejle/Lillebaelt Hospital; Department of Clinical Genetics, Vejle/Lillebaelt
Hospital; Department of Social Medicine, Danish Aging Research Center,
University of Copenhagen
Background:
Telomeres, the very end of our DNA, are specialized structures
that protect our chromosomes from degradation. Critically short telomeres
induce cellular senescence and have recently been suggested to play a role in
chondrocyte senescence in OA knees. Ultra-short telomeres are the prevailing
product of stress-induced telomere shortening, suggesting that oxidative
damage to chondrocytes might initiate OA.
Purpose / Aim of Study:
To investigate the relationship between short
telomeres and OA in human femoral heads, including the possible role of short
telomeres in natural aging of cartilage.
Materials and Methods:
23
human femoral heads were obtained from 14
patients diagnosed with primary OA and 9 controls having suffered a displaced
medial femoral neck fracture. Articular cartilage from zones differing in
distance from the lesion site was obtained and split into three parts: one for
telomere length measurements, one for OA grading, and one for
immunohistochemical staining.
Findings / Results:
Load of ultra-short telomeres increased closer to the lesion
site and correlated with OA severity in both OA samples (R = 0.72, P =
0.0017)
and fracture samples (R = 0.62, P = 0.0015). Mean telomere length
correlated with OA severity in OA samples (R = -0.27, P = 0.047), but not in
fracture samples (R = -0.28, P = 0.10). Mean telomere length decreased closer
to the lesion site, however, unexpectedly increased in the zone nearest the
lesion. This increase was associated with findings of cells expressing markers
characteristic of progenitor-like cells.
Conclusions:
These in vivo studies suggest a role of ultra-short telomeres in
the pathology of OA and in natural aging of cartilage. Our findings further
suggest that progenitor-like cells with long telomeres are recruited to the most
damaged cartilage regions possibly in an attempt to repair the OA affected
tissue.
