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Arthritis Research and Therapy

, 14:R12

First Online: 18 January 2012Received: 17 July 2011Revised: 17 November 2011Accepted: 18 January 2012

Abstract

IntroductionTelomere 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.

MethodsSamples 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.

ResultsThe 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.

ConclusionsThese in vivo data, especially the quantification of ultra-short telomeres, stress a role of telomere shortening in human OA.

Abbreviationsbpbase pairs

OAosteoarthritis

PCRpolymerase chain reaction

Q-FISHquantitative fluorescence in situ hybridization

SA β-galsenescence-associated β-galactosidase

SAHFsenescence-associated heterochromatin foci

STELAsingle telomere length assay.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3687 contains supplementary material, which is available to authorized users.

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Autor: Maria Harbo - Laila Bendix - Anne-Christine Bay-Jensen - Jesper Graakjaer - Kent Søe - Thomas L Andersen - Per Kjaersgaar

Fuente: https://link.springer.com/



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