Department of Clinical Genetics, Vejle/Lillebaelt Hospital, Kabbeltoft 25, 7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, J.B. Winsloews Vej 19,3., 5000 Odense C, Denmark; Danish Aging Research Center, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark.
Mech Ageing Dev. 2013 Sep;134(9):367-72. doi: 10.1016/j.mad.2013.07.002. Epub 2013 Jul 18.
Ultra-short telomeres caused by stress-induced telomere shortening are suggested to induce chondrocyte senescence in human osteoarthritic knees. Here we have further investigated the role of ultra-short telomeres in the development of osteoarthritis (OA) and in aging of articular cartilage in human hips.
Cartilage was obtained from four different distances of the central weight-bearing area in human femoral heads (14 OA and 9 non-OA). Samples were split into three: one for quantification of ultra-short single telomeres by Universal STELA and mean telomere length measurement by Q-PCR; one for histological grading of OA, and one for immunohistochemical staining.
Load of ultra-short telomeres increased closer to the central weight-bearing area and correlated with cartilage degradation in both OA and non-OA samples. Mean telomere length decreased with decreasing distance to the central weight-bearing area, however, unexpectedly increased in the most central zone. This increase was associated with immunohistochemical findings of cells expressing markers characteristic of progenitor-like cells.
These findings suggest a role of short telomeres in the development of OA and in aging of articular cartilage. Furthermore, progenitor-like cells with long telomeres may be recruited to the most damaged areas of the cartilage.
压力诱导的端粒缩短导致的超短端粒被认为会诱导人类骨关节炎膝关节中的软骨细胞衰老。在这里，我们进一步研究了超短端粒在骨关节炎（OA）发展以及人类髋关节软骨老化中的作用。
从人类股骨头中央承重区的四个不同距离处获取软骨（14 个 OA 样本和 9 个非 OA 样本）。样本分为三份：一份用于通过通用 STELA 定量超短单端粒，另一份用于通过 Q-PCR 测量平均端粒长度，还有一份用于组织学分级和免疫组织化学染色。
超短端粒的负荷随着靠近中央承重区而增加，并且与 OA 和非 OA 样本中的软骨降解相关。平均端粒长度随着距中央承重区距离的减小而减小，但在最中央区域出人意料地增加。这种增加与表达祖细胞样细胞特征标志物的细胞的免疫组织化学发现相关。
这些发现表明短端粒在 OA 的发展和关节软骨老化中发挥作用。此外，具有长端粒的祖细胞样细胞可能被招募到软骨受损最严重的区域。
