The distribution pattern of critically short telomeres in human osteoarthritic knees

Harbo M, Bendix L, Bay-Jensen AC, Graakjaer J, Søe K, Andersen TL, Kjaersgaard-Andersen P, Koelvraa S, Delaisse JM · Arthritis Res Ther

The load of ultra-short telomeres rose towards the lesion in 19 of 20 paired directions, with the twentieth pair identical (P = 0.000004); Mankin score rose in all 21 pairs and senescence in 20 of 21. Mean telomere length fell towards the lesion in 17 of 21 pairs (P = 0.007), a weaker pattern. Both telomere measures correlated with osteoarthritis grade and senescence level, and the ultra-short-telomere load correlated more closely than mean length did.

Population

Tibial plateaus from three post-menopausal women aged 56, 62 and 67 undergoing knee replacement for bilateral osteoarthritis, biopsied at paired positions close to and away from the central lesion in four directions

Intervention

Measurement of ultra-short single telomeres (under 1,500 base pairs) by Universal STELA, mean telomere length by Q-FISH, senescence by senescence-associated heterochromatin foci, and osteoarthritis grade by Mankin score, in cartilage as taken rather than after culture

Comparator

Paired biopsies away from the lesion in the same joint

Limitations

Three knees from three women, all end-stage; associations within a joint say nothing about cause; the authors declare no conflict of interest and the text carries no funding statement. The first in-vivo measurement of the telomere subpopulation thought to drive chondrocyte senescence, and the study the later reviews lean on for the claim that telomere loss tracks the lesion.