Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice
Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice
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DOI：
10.1096/fj.201600918r
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发表时间：
2017-03-01
期刊：
影响因子：
4.8
通讯作者：
Chagin, Andrei S.
中科院分区：
文献类型：
--
作者：
Li, Lei;Newton, Phillip T.;Chagin, Andrei S.
关节软骨几乎没有再生能力。最近，遗传谱系追踪实验揭示了关节表面的软骨细胞祖细胞。我们通过使用体内遗传方法进一步表征了这些祖细胞。组蛋白H2 B-绿色荧光蛋白滞留显示，表层细胞分裂比底层关节软骨细胞慢。克隆遗传追踪结合免疫组化显示，表层细胞更新其数量的对称分裂，表达间充质干细胞标志物，并产生软骨细胞通过不对称和对称分化。细胞动力学的定量分析，结合磷钨酸增强的显微计算机断层扫描，表明表面细胞产生软骨细胞，并有助于关节软骨的生长和重塑。此外，我们发现，软骨更新发生在出生后早期，表层细胞的后代完全取代胎儿软骨细胞。因此，表面细胞是自我更新的祖细胞，能够维持其自身的群体并满足单能成体干细胞的标准。此外，这些细胞的后代从头重建成人关节软骨，完全取代胎儿软骨细胞。
Articular cartilage has little regenerative capacity. Recently, genetic lineage tracing experiments have revealed chondrocyte progenitors at the articular surface. We further characterized these progenitors by using in vivo genetic approaches. Histone H2B-green fluorescent protein retention revealed that superficial cells divide more slowly than underlying articular chondrocytes. Clonal genetic tracing combined with immunohistochemistry revealed that superficial cells renew their number by symmetric division, express mesenchymal stem cell markers, and generate chondrocytes via both asymmetric and symmetric differentiation. Quantitative analysis of cellular kinetics, in combination with phosphotungstic acid- enhanced micro-computed tomography, showed that superficial cells generate chondrocytes and contribute to the growth and reshaping of articular cartilage. Furthermore, we found that cartilage renewal occurs as the progeny of superficial cells fully replace fetal chondrocytes during early postnatal life. Thus, superficial cells are self-renewing progenitors that are capable of maintaining their own population and fulfilling criteria of unipotent adult stem cells. Furthermore, the progeny of these cells reconstitute adult articular cartilage de novo, entirely substituting fetal chondrocytes.