Chondrocytes in the resting zone of the growth plate are maintained in a Wnt-inhibitory environment.
Chondrocytes in the resting zone of the growth plate are maintained in a Wnt-inhibitory environment.
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作者：
Hallett SA;Matsushita Y;Ono W;Sakagami N;Mizuhashi K;Tokavanich N;Nagata M;Zhou A;Hirai T;Kronenberg HM;Ono N
出生后生长板静止区的软骨细胞的特征在于缓慢的细胞周期进程，并包含一群表达甲状旁腺相关蛋白（PTHrP）的骨骼干细胞，其有助于柱状软骨细胞的形成。然而，这些软骨细胞如何维持在静止区仍然不确定。我们进行了一个遗传脉冲追踪的方法来分离慢循环，标签保留软骨细胞（LRC）使用软骨细胞特异性强力霉素可控Tet-Off系统调节组蛋白2B连接的GFP的表达。比较RNA-seq分析分别鉴定了LRC和非LRC中Wnt信号传导的抑制剂和激活剂的显著富集。使用Pthlh-creER和Apc-floxed等位基因激活PTHrP+静息软骨细胞中的Wnt/β-连环蛋白信号传导损害了它们形成柱状软骨细胞的能力。因此，慢循环软骨细胞维持在静息区内的Wnt抑制环境中，揭示了调节出生后生长板的PTHrP+骨骼干细胞的维持和分化的新机制。
Chondrocytes in the resting zone of the postnatal growth plate are characterized by slow cell cycle progression, and encompass a population of parathyroid hormone-related protein (PTHrP)-expressing skeletal stem cells that contribute to the formation of columnar chondrocytes. However, how these chondrocytes are maintained in the resting zone remains undefined. We undertook a genetic pulse-chase approach to isolate slow cycling, label-retaining chondrocytes (LRCs) using a chondrocyte-specific doxycycline-controllable Tet-Off system regulating expression of histone 2B-linked GFP. Comparative RNA-seq analysis identified significant enrichment of inhibitors and activators for Wnt signaling in LRCs and non-LRCs, respectively. Activation of Wnt/β-catenin signaling in PTHrP+ resting chondrocytes using Pthlh-creER and Apc-floxed allele impaired their ability to form columnar chondrocytes. Therefore, slow-cycling chondrocytes are maintained in a Wnt-inhibitory environment within the resting zone, unraveling a novel mechanism regulating maintenance and differentiation of PTHrP+ skeletal stem cells of the postnatal growth plate.