The distribution pattern of critically short telomeres in human osteoarthritic knees

TY - JOUR

T1 - The distribution pattern of critically short telomeres in human osteoarthritic knees

AU - Harbo, Maria

AU - Bendix, Laila

AU - Bay-Jensen, Anne Christine

AU - Graakjaer, Jesper

AU - Søe, Kent

AU - Levin Andersen, Thomas

AU - Kjaersgaard-Andersen, Per

AU - Koelvraa, Steen

AU - Delaisse, Jean-Marie

PY - 2012/1/18

Y1 - 2012/1/18

N2 - Introduction: Telomere shortening is associated with a number of common age-related diseases. A role of telomere shortening in osteoarthritis (OA) has been suggested, mainly based on the assessment of mean telomere length in ex vivo expanded chondrocytes. We addressed this role directly in vivo by using a newly developed assay, which measures specifically the load of ultra-short single telomeres (below 1,500 base pairs), that is, the telomere subpopulation believed to promote cellular senescence.Methods: Samples were obtained from human OA knees at two distances from the central lesion site. Each sample was split into three: one was used for quantification of ultra-short single telomeres through the Universal single telomere length assay (STELA), one for histological Mankin grading of OA, and one for mean telomere length measurement through quantitative fluorescence in situ hybridization (Q-FISH) as well as for assessment of senescence through quantification of senescence-associated heterochromatin foci (SAHF).Results: The load of ultra-short telomeres as well as mean telomere length was significantly associated with proximity to lesions, OA severity, and senescence level. The degree of significance was higher when assessed through load of ultra-short telomeres per cell compared with mean telomere length.Conclusions: These in vivo data, especially the quantification of ultra-short telomeres, stress a role of telomere shortening in human OA.

AB - Introduction: Telomere shortening is associated with a number of common age-related diseases. A role of telomere shortening in osteoarthritis (OA) has been suggested, mainly based on the assessment of mean telomere length in ex vivo expanded chondrocytes. We addressed this role directly in vivo by using a newly developed assay, which measures specifically the load of ultra-short single telomeres (below 1,500 base pairs), that is, the telomere subpopulation believed to promote cellular senescence.Methods: Samples were obtained from human OA knees at two distances from the central lesion site. Each sample was split into three: one was used for quantification of ultra-short single telomeres through the Universal single telomere length assay (STELA), one for histological Mankin grading of OA, and one for mean telomere length measurement through quantitative fluorescence in situ hybridization (Q-FISH) as well as for assessment of senescence through quantification of senescence-associated heterochromatin foci (SAHF).Results: The load of ultra-short telomeres as well as mean telomere length was significantly associated with proximity to lesions, OA severity, and senescence level. The degree of significance was higher when assessed through load of ultra-short telomeres per cell compared with mean telomere length.Conclusions: These in vivo data, especially the quantification of ultra-short telomeres, stress a role of telomere shortening in human OA.

U2 - 10.1186/ar3687

DO - 10.1186/ar3687

M3 - Journal article

C2 - 22257826

SN - 1478-6354

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

ER -