The ontogeny and fate of stem cells have been extensively investigated by lineage-tracing approaches. At distinct anatomical sites, bone tissue harbors multiple types of skeletal stem cells, which may independently supply osteogenic cells in a site-specific manner. Periosteal stem cells (PSCs) and growth plate resting zone stem cells (RZSCs) critically contribute to intramembranous and endochondral bone formation, respectively. However, it remains unclear whether there is functional crosstalk between these two types of skeletal stem cells. Here we show PSCs are not only required for intramembranous bone formation, but also for the growth plate maintenance and prolonged longitudinal bone growth. Mice deficient in PSCs display progressive defects in intramembranous and endochondral bone formation, the latter of which is caused by a deficiency in PSC-derived Indian hedgehog (Ihh). PSC-specific deletion of Ihh impairs the maintenance of the RZSCs, leading to a severe defect in endochondral bone formation in postnatal life. Thus, crosstalk between periosteal and growth plate stem cells is essential for post-developmental skeletal growth.

干细胞的个体发育和命运已通过谱系追踪方法进行了广泛的研究。在不同的解剖部位，骨组织含有多种类型的骨骼干细胞，它们可以以特定部位的方式独立地提供成骨细胞。骨膜干细胞 (PSCs) 和生长板静息区干细胞 (RZSCs) 分别对膜内和软骨内骨形成至关重要。然而，目前尚不清楚这两种骨骼干细胞之间是否存在功能性串扰。在这里，我们显示 PSC 不仅是膜内骨形成所必需的，而且也是生长板维持和延长纵向骨生长所必需的。缺乏 PSC 的小鼠在膜内和软骨内骨形成中表现出进行性缺陷，后者是由 PSC 衍生的印度刺猬 (Ihh) 缺乏引起的。PSC 特异性 Ihh 缺失会损害 RZSCs 的维持，导致出生后软骨内骨形成的严重缺陷。因此，骨膜和生长板干细胞之间的串扰对于发育后骨骼生长至关重要。