Open Access Highly Accessed Research article

The distribution pattern of critically short telomeres in human osteoarthritic knees

Maria Harbo12*, Laila Bendix24, Anne-Christine Bay-Jensen1, Jesper Graakjaer2, Kent Søe1, Thomas L Andersen1, Per Kjaersgaard-Andersen3, Steen Koelvraa24 and Jean-Marie Delaisse1

Author Affiliations

1 Department of Clinical Cell Biology, Vejle/Lillebaelt Hospital, Institute of Regional Health Research, University of Southern Denmark, Kabbeltoft 25, 7100 Vejle, Denmark

2 Department of Clinical Genetics, Vejle/Lillebaelt Hospital, Institute of Regional Health Research, University of Southern Denmark, Kabbeltoft 25, 7100 Vejle, Denmark

3 Department of Orthopedic Surgery, Vejle/Lillebaelt Hospital, Institute of Regional Health Research, University of Southern Denmark, Kabbeltoft 25, 7100 Vejle, Denmark

4 Danish Aging Research Center, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark

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Arthritis Research & Therapy 2012, 14:R12  doi:10.1186/ar3687

Published: 18 January 2012

Abstract

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.