the distribution pattern of critically short telomeres in human osteoarthritic knees非常短的端粒的分布模式在人类骨关节炎的膝盖.pdf

Harbo et al. Arthritis Research Therapy 2012, 14:R12 /content/14/1/R12 RESEARCH ARTICLE Open Access The distribution pattern of critically short telomeres in human osteoarthritic knees 1,2* 2,4 1 2 1 1 Maria Harbo , Laila Bendix , Anne-Christine Bay-Jensen , Jesper Graakjaer , Kent Søe , Thomas L Andersen , Per Kjaersgaard-Andersen3, Steen Koelvraa2,4 and Jean-Marie Delaisse1 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 telomer