The fate of early perichondrial cells in developing bones.
The fate of early perichondrial cells in developing bones.
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DOI：
10.1038/s41467-022-34804-6
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发表时间：
2022-11-28
影响因子：
16.6
通讯作者：
Ono, Noriaki
中科院分区：
文献类型：
--
作者：
Matsushita, Yuki;Chu, Angel Ka Yan;Tsutsumi-Arai, Chiaki;Orikasa, Shion;Nagata, Mizuki;Wong, Sunny Y.;Welch, Joshua D.;Ono, Wanida;Ono, Noriaki
在软骨内骨发育中，成骨细胞和骨髓基质细胞在胎儿软骨及其周围的软骨膜中具有双重来源。然而，早期软骨膜细胞如何独特地促进骨骼发育仍未确定。在这里，我们使用体内细胞谱系分析表明，Dlx 5-creER标记的Dlx 5+胎儿软骨膜细胞不产生软骨，但可持续地有助于皮质骨和骨髓基质隔室的方式互补的胎儿软骨细胞衍生物的调节下的刺猬信号。出生后，Dlx 5+胎儿软骨膜细胞衍生物优先填充骨干骨髓基质与休眠的脂肪细胞偏向的状态，是难治性甲状旁腺囊肿诱导的骨愈合。因此，胎儿软骨的早期软骨膜细胞注定要成为出生后骨干骨髓中基质细胞的成脂亚群，这支持了成人骨髓基质隔室在胎儿骨原基的两种不同起源细胞内发育规定的理论。在软骨内骨发育中，成骨细胞和骨髓基质细胞在胎儿软骨及其周围的软骨膜中具有双重来源。在这里，他们表明软骨膜细胞注定要成为脂肪细胞偏向的基质细胞，表明骨髓基质隔室是由它们的起源细胞定义的。
In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5+ fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling. Postnatally, Dlx5+ fetal perichondrial cell derivatives preferentially populate the diaphyseal marrow stroma with a dormant adipocyte-biased state and are refractory to parathyroid hormone-induced bone anabolism. Therefore, early perichondrial cells of the fetal cartilage are destined to become an adipogenic subset of stromal cells in postnatal diaphyseal bone marrow, supporting the theory that the adult bone marrow stromal compartments are developmentally prescribed within the two distinct cells-of-origins of the fetal bone anlage. In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. Here they show that perichondrial cells are destined to become adipocyte-biased stromal cells, indicating that marrow stromal compartments are defined by their cells of origin.
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通讯作者：
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