Distribution of slow-cycling cells in epiphyseal cartilage and requirement of β-catenin signaling for their maintenance in growth plate.

Distribution of slow-cycling cells in epiphyseal cartilage and requirement of β-catenin signaling for their maintenance in growth plate.
复制标题

慢循环细胞在附后软骨中的分布以及β-catenin信号在生长板中维持的需求。

DOI:
10.1002/jor.22583
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发表时间:
2014-05
影响因子:
2.8
通讯作者:
Enomoto-Iwamoto, Motomi
Enomoto-Iwamoto, Motomi
中科院分区:
医学3区
文献类型:
--
作者:
Candela, Maria Elena;Cantley, Leslie;Yasuaha, Rika;Iwamoto, Masahiro;Pacifici, Maurizio;Enomoto-Iwamoto, Motomi

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增殖缓慢是干细胞的特征之一。我们使用一种新的核苷衍生物5-乙炔基-2 '-脱氧尿苷(EdU)的脉冲追踪方法,研究了发育和生长骨骼中慢周期细胞的存在、分布和调节。C57 BL/6小鼠从出生后第4天至第7天每天接受EdU的腹膜内注射。最后一次EdU注射后一天,标记关节软骨和生长板中的大量细胞。最后一次注射后6周,EdU标记的细胞数量明显减少,但仍有少量细胞主要分布在关节面,且关节面的标记指数明显高于关节软骨的其余部分。在生长板中,大多数EdU阳性细胞位于次级骨化中心正下方的顶层。有趣的是,出生后软骨中β-连环蛋白的条件性消融导致生长板中EdU标记的细胞完全丧失,显示出组织混乱和功能障碍。总之,我们的数据表明,慢循环细胞确实存在于关节软骨和生长板的特定位置和数量。β-连环蛋白信号通路似乎在维持慢循环细胞方面发挥了以前未预料到的作用。
Slow proliferation is one of characteristics of stem cells. We examined the presence, distribution and regulation of slow-cycling cells in the developing and growing skeleton using a pulse-chase method with a new nucleoside derivative, 5-ethynyl-2’-deoxyuridine (EdU). C57BL/6 mice received daily intraperitoneal injections of EdU from postnatal day 4 to day 7. One day after the last EdU injection, a large population of cells in articular cartilage and growth plate was labeled. Six weeks after the last injection, the number of EdU-labeled cells dramatically decreased, but a small number of them were dominantly present in the articular surface, and the labeling index was significantly higher in the surface than that in the rest of articular cartilage. In the growth plate, most EdU-positive cells were found in the top layer that lies immediately below the secondary ossification center. Interestingly, postnatal conditional ablation of β-catenin in cartilage caused a complete loss of the EdU-labeled cells in growth plate that displayed disorganization and dysfunction. Together, our data demonstrate that slow-cycling cells do reside in specific locations and numbers in both articular cartilage and growth plate. The β-catenin signaling pathway appears to play a previously unsuspected role in maintenance of the slow-cycling cells.
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