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Identifying the mesenchymal progenitors that drive fetal bone growth


Ono et al. performed fate-mapping studies to discover the source of fetal mesenchymal stem cells that differentiate into the cells responsible for endochrondal bone development.

The collagen II (Col2) promoter/enhancers Col2-crel and Col2-creER were expressed in mice within osteoblast progenitor cells during fetal growth. Formation of these cells did not require Runx2 but this was needed to drive their differentiation into osteoblasts.

Mapping studies further revealed that these cells are present very early in fetal development, generating osteoblasts, stromal cells and chondrocytes within the bone growth plates and articular cartilage. In contrast, cells expressing creER driven by the promoter/enhancers Sox9 and aggrecan, differentiate into osteoblasts but after a short time develop into stromal cells that then persist in the bone marrow, generating new cells for about 12 months.

All the progenitor cell types identified appear to regulate the extremely rapid bone growth that occurs during fetal development and are distinct from the progenitors responsible for generating osteoblasts, chondrocytes and other stromal cells during adult life.

Editor’s comment: This elegant study using lineage-tracing experiments revealed that Sox9- and Col2-expressing cells are precursors for chondrocytes and also for osteoblasts, stromal cells and adipocytes during fetal growth. These cells are distinct from adult mesenchymal progenitors. It will be important to clarify the relationship between these progenitors that are active during rapid bone growth and adult BMSCs, which contribute to much slower bone remodeling.

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