Multiple distinct types of skeletal progenitors have been shown to contribute to endochondral bone development and maintenance. However, the division of labor and hierarchical relationship between different progenitor populations remain undetermined. Here we developed dual-recombinase fate-mapping systems to capture the skeletal progenitor transition during postnatal bone formation. We showed that postnatal osteoblasts arose primarily from chondrocytes before adolescence and from Lepr⁺ bone marrow stromal cells (BMSCs) after adolescence. This transition occurred in the diaphysis during adolescence and progressively spread to the metaphysis. The osteoblast-forming Lepr⁺ BMSCs derived primarily from fetal Col2⁺ cells. Conditional deletion of Runx2 from perinatal chondrocytes and adult Lepr⁺ BMSCs impaired bone lengthening and thickening, respectively. Forced running increased osteoblast formation by perinatal chondrocytes but not by adult Lepr⁺ BMSCs. Thus, the short-term developmental skeletal progenitors generated the long-term adult skeletal progenitors. They sequentially control the growth and maintenance of endochondral bones.

多种不同类型的骨骼祖细胞已被证明有助于软骨内骨的发育和维持。然而，不同祖先种群之间的分工和等级关系仍未确定。在这里，我们开发了双重组酶命运映射系统来捕捉出生后骨形成过程中的骨骼祖细胞转变。我们发现，出生后成骨细胞主要来自青春期前的软骨细胞和青春期后的Lepr ⁺骨髓基质细胞 (BMSCs)。这种转变在青春期发生在骨干，并逐渐扩散到干骺端。主要来自胎儿Col2 ⁺的成骨细胞形成Lepr ⁺ BMSCs细胞。从围产期软骨细胞和成人Lepr ⁺ BMSCs条件性删除Runx2分别损害骨延长和增厚。强迫跑步增加了围产期软骨细胞的成骨细胞形成，而不是成人Lepr ⁺ BMSCs。因此，短期发育骨骼祖细胞产生了长期成人骨骼祖细胞。它们依次控制软骨内骨骼的生长和维持。