Uncovering the cellular and molecular changes in tendon stem/progenitor cells attributed to tendon aging and degeneration.
Uncovering the cellular and molecular changes in tendon stem/progenitor cells attributed to tendon aging and degeneration.
复制标题
DOI：
10.1111/acel.12124
复制
发表时间：
2013-12
期刊：
影响因子：
7.8
通讯作者：
Docheva D
中科院分区：
文献类型：
--
作者：
Kohler J;Popov C;Klotz B;Alberton P;Prall WC;Haasters F;Müller-Deubert S;Ebert R;Klein-Hitpass L;Jakob F;Schieker M;Docheva D
虽然干细胞特性改变和组织衰老之间的联系已经被认识到，但肌腱衰老的分子和细胞过程尚未阐明。由于肌腱含有干/祖细胞（TSPC），我们研究了TSPC的分子和细胞属性是否在肌腱老化和退化过程中发生变化。比较来自年轻/健康（Y-TSPC）和老年/退化的人跟腱活检（A-TSPC）的TSPC，我们观察到A-TSPC表现出深刻的自我更新和克隆缺陷，而它们的多能性仍然保留。衰老分析表明，过早进入衰老的A-TSPC，伴随着p16 INK 4A的上调的发现。为了确定年龄相关的分子因素，我们进行了微阵列和基因本体分析。这些分析揭示了A-TSPC中一个有趣的转录组转变，其中最差异表达的探针组编码调节细胞粘附、迁移和肌动蛋白细胞骨架的基因。时间推移分析表明，A-TSPC表现出减速运动和延迟伤口闭合伴随着较高的肌动蛋白应力纤维含量和较慢的周转肌动蛋白丝。最后，基于微阵列候选人的表达分析，我们认为，失调的细胞-基质相互作用和ROCK激酶通路可能是TSPC老化的关键球员。综上所述，我们认为在肌腱老化和退化过程中，TSPC池在大小和功能适应性方面正在耗尽。因此，我们的研究为进一步探索肌腱老化和变性背后的分子机制以及选择新的肌腱特异性治疗靶点提供了第一个基本基础。
Although the link between altered stem cell properties and tissue aging has been recognized, the molecular and cellular processes of tendon aging have not been elucidated. As tendons contain stem/progenitor cells (TSPC), we investigated whether the molecular and cellular attributes of TSPC alter during tendon aging and degeneration. Comparing TSPC derived from young/healthy (Y-TSPC) and aged/degenerated human Achilles tendon biopsies (A-TSPC), we observed that A-TSPC exhibit a profound self-renewal and clonogenic deficits, while their multipotency was still retained. Senescence analysis showed a premature entry into senescence of the A-TSPC, a finding accompanied by an upregulation of p16INK4A. To identify age-related molecular factors, we performed microarray and gene ontology analyses. These analyses revealed an intriguing transcriptomal shift in A-TSPC, where the most differentially expressed probesets encode for genes regulating cell adhesion, migration, and actin cytoskeleton. Time-lapse analysis showed that A-TSPC exhibit decelerated motion and delayed wound closure concomitant to a higher actin stress fiber content and a slower turnover of actin filaments. Lastly, based on the expression analyses of microarray candidates, we suggest that dysregulated cell–matrix interactions and the ROCK kinase pathway might be key players in TSPC aging. Taken together, we propose that during tendon aging and degeneration, the TSPC pool is becoming exhausted in terms of size and functional fitness. Thus, our study provides the first fundamental basis for further exploration into the molecular mechanisms behind tendon aging and degeneration as well as for the selection of novel tendon-specific therapeutical targets.
登录
查看更多内容
影响因子：
4.6
作者：
Pryce, Brian A.;Watson, Spencer S.;Schweitzer, Ronen
通讯作者：
Schweitzer, Ronen
影响因子：
9
作者：
通讯作者：
--
DOI：
10.1083/jcb.201010131
发表时间：
2011-04-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Liu L;Rando TA
通讯作者：
Rando TA
影响因子：
20.3
作者：
Ng, Felicia;Boucher, Shayne;Tanavde, Vivek
通讯作者：
Tanavde, Vivek
影响因子：
64.8
作者：
Molofsky, Anna V.;Slutsky, Shalom G.;Morrison, Sean J.
通讯作者：
Morrison, Sean J.