Embryonic origin and Hox status determine progenitor cell fate during adult bone regeneration

Philipp Leucht, Jae Beom Kim, Raimy Amasha, Aaron W. James, Sabine Girod, Jill A. Helms

Research output: Contribution to journalArticlepeer-review

Abstract

The fetal skeleton arises from neural crest and from mesoderm. Here, we provide evidence that each lineage contributes a unique stem cell population to the regeneration of injured adult bones. Using Wnt1Cre::ZIEG mice we found that the neural crest-derived mandible heals with neural crest-derived skeletal stem cells, whereas the mesoderm-derived tibia heals with mesoderm-derived stem cells. We tested whether skeletal stem cells from each lineage were functionally interchangeable by grafting mesoderm-derived cells into mandibular defects, and vice versa. All of the grafting scenarios, except one, healed through the direct differentiation of skeletal stem cells into osteoblasts; when mesoderm-derived cells were transplanted into tibial defects they differentiated into osteoblasts but when transplanted into mandibular defects they differentiated into chondrocytes. A mismatch between the Hox gene expression status of the host and donor cells might be responsible for this aberration in bone repair. We found that initially, mandibular skeletal progenitor cells are Hox-negative but that they adopt a Hoxa 11-positive profile when transplanted into a tibial defect. Conversely, tibial skeletal progenitor cells are Hox-positive and maintain this Hox status even when transplanted into a Hox-negative mandibular defect. Skeletal progenitor cells from the two lineages also show differences in osteogenic potential and proliferation, which translate into more robust in vivo bone regeneration by neural crest-derived cells. Thus, embryonic origin and Hox gene expression status distinguish neural crest-derived from mesoderm-derived skeletal progenitor cells, and both characteristics influence the process of adult bone regeneration.

Original languageEnglish (US)
Pages (from-to)2845-2854
Number of pages10
JournalDevelopment
Volume135
Issue number17
DOIs
StatePublished - Sep 2008

Keywords

  • Chondrocyte
  • Graft
  • Mesoderm
  • Mouse
  • Neural crest
  • Osteoblast
  • Periosteum

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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