A Subset of Chondrogenic Cells Provides Early Mesenchymal Progenitors in Growing Bones

Nat Cell Biol. 2014 Dec;16(12):1157-67. doi: 10.1038/ncb3067. Epub 2014 Nov 24.

Abstract

The hallmark of endochondral bone development is the presence of cartilaginous templates, in which osteoblasts and stromal cells are generated to form mineralized matrix and support bone marrow haematopoiesis. However, the ultimate source of these mesenchymal cells and the relationship between bone progenitors in fetal life and those in later life are unknown. Fate-mapping studies revealed that cells expressing cre-recombinases driven by the collagen II (Col2) promoter/enhancer and their descendants contributed to, in addition to chondrocytes, early perichondrial precursors before Runx2 expression and, subsequently, to a majority of osteoblasts, Cxcl12 (chemokine (C-X-C motif) ligand 12)-abundant stromal cells and bone marrow stromal/mesenchymal progenitor cells in postnatal life. Lineage-tracing experiments using a tamoxifen-inducible creER system further revealed that early postnatal cells marked by Col2-creER, as well as Sox9-creER and aggrecan (Acan)-creER, progressively contributed to multiple mesenchymal lineages and continued to provide descendants for over a year. These cells are distinct from adult mesenchymal progenitors and thus provide opportunities for regulating the explosive growth that occurs uniquely in growing mammals.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aggrecans / genetics
  • Animals
  • Bone Density Conservation Agents / pharmacology
  • Bone Development / physiology*
  • Bone Marrow Cells / metabolism
  • Bone and Bones / embryology*
  • Cell Differentiation
  • Cell Lineage / genetics
  • Cell Proliferation
  • Chemokine CXCL12 / biosynthesis
  • Chondrocytes / cytology*
  • Collagen Type II / genetics
  • Core Binding Factor Alpha 1 Subunit / biosynthesis
  • Embryo, Mammalian / cytology
  • Enhancer Elements, Genetic
  • Green Fluorescent Proteins / genetics
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Transgenic
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Promoter Regions, Genetic
  • Sp7 Transcription Factor
  • Tamoxifen / pharmacology
  • Transcription Factors / genetics

Substances

  • Aggrecans
  • Bone Density Conservation Agents
  • Chemokine CXCL12
  • Collagen Type II
  • Core Binding Factor Alpha 1 Subunit
  • Cxcl12 protein, mouse
  • Runx2 protein, mouse
  • Sp7 Transcription Factor
  • Sp7 protein, mouse
  • Transcription Factors
  • Tamoxifen
  • Green Fluorescent Proteins