Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence.
Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence.
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DOI：
10.1038/srep41421
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发表时间：
2017-02-02
影响因子：
4.6
通讯作者：
Khan IM
中科院分区：
文献类型：
--
作者：
Fellows CR;Williams R;Davies IR;Gohil K;Baird DM;Fairclough J;Rooney P;Archer CW;Khan IM
近年来，越来越清楚的是，关节软骨含有一个可行的祖细胞库，并且兴趣集中在它们在发育和疾病期间的作用上。使用荧光激活分选技术的祖细胞数量的分析已经导致了广泛的估计，这可能是细胞表面标志物的上下文依赖性表达的结果。我们使用集落形成试验来可靠地确定正常和骨关节炎软骨中的软骨祖细胞数量，我们观察到病变组织中软骨祖细胞数量增加2倍（P < 0.0001）。有趣的是，来自骨关节炎软骨的单个和多个供体的克隆分离物的细胞动力学分析揭示了存在以早期衰老表型为特征的不同祖细胞亚群。不同的亚群表现出衰老相关的β-半乳糖苷酶活性增加，平均端粒长度较低，但保留了进行多谱系分化的能力。骨关节炎是一种与年龄相关的疾病，细胞衰老被预测为病理过程的重要组成部分。这项研究表明，虽然早期衰老是一个子集的激活祖细胞的固有特性，也有一个池的祖细胞与延长生存能力和再生潜力驻留在骨关节炎软骨。
In recent years it has become increasingly clear that articular cartilage harbours a viable pool of progenitor cells and interest has focussed on their role during development and disease. Analysis of progenitor numbers using fluorescence-activated sorting techniques has resulted in wide-ranging estimates, which may be the result of context-dependent expression of cell surface markers. We have used a colony-forming assay to reliably determine chondroprogenitor numbers in normal and osteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P < 0.0001). Intriguingly, cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilage revealed the presence of a divergent progenitor subpopulation characterised by an early senescent phenotype. Divergent sub-populations displayed increased senescence-associated β–galactosidase activity, lower average telomere lengths but retained the capacity to undergo multi-lineage differentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be a significant component of the pathological process. This study shows that although early senescence is an inherent property of a subset of activated progenitors, there is also a pool of progenitors with extended viability and regenerative potential residing within osteoarthritic cartilage.