Genetic analysis of Runx2 function during intramembranous ossification

Takeshi Takarada, Ryota Nakazato, Azusa Tsuchikane, Koichi Fujikawa, Takashi Iezaki, Yukio Yoneda, Eiichi Hinoi

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Runt-related transcription factor 2 (Runx2) is an essential transcriptional regulator of osteoblast differentiation and its haploinsufficiency leads to cleidocranial dysplasia because of a defect in osteoblast differentiation during bone formation through intramembranous ossification. The cellular origin and essential period for Runx2 function during osteoblast differentiation in intramembranous ossification remain poorly understood. Paired related homeobox 1 (Prx1) is expressed in craniofacial mesenchyme, and Runx2 deficiency in cells of the Prx1 lineage (in mice referred to here as Runx2prx1−/−) resulted in defective intramembranous ossification. Runx2 was heterogeneously expressed in Prx1-GFP+ cells located at the intrasutural mesenchyme in the calvaria of transgenic mice expressing GFP under the control of the Prx1 promoter. Double-positive cells for Prx1- GFP and stem cell antigen-1 (Sca1) (Prx1+Sca1+ cells) in the calvaria expressed Runx2 at lower levels and were more homogeneous and primitive than Prx1+Sca1 cells. Osterix (Osx) is another transcriptional determinant of osteoblast lineages expressed by osteoblast precursors; Osx is highly expressed by Prx1−Runx2+ cells at the osteogenic front and on the surface of mineralized bone in the calvaria. Runx2 deficiency in cells of the Osx lineage (in mice referred to here as Runx2osx−/−) resulted in severe defects in intramembranous ossification. These findings indicate that the essential period of Runx2 function in intramembranous ossification begins at the Prx1+Sca1+ mesenchymal stem cell stage and ends at the Osx+Prx1Sca1 osteoblast precursor stage.

Original languageEnglish
Pages (from-to)211-218
Number of pages8
JournalDevelopment (Cambridge)
Volume143
Issue number2
DOIs
Publication statusPublished - Jan 15 2016

Keywords

  • Mouse
  • Nestin
  • Osteoblast
  • Osterix
  • Prx1
  • Runx2

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Takarada, T., Nakazato, R., Tsuchikane, A., Fujikawa, K., Iezaki, T., Yoneda, Y., & Hinoi, E. (2016). Genetic analysis of Runx2 function during intramembranous ossification. Development (Cambridge), 143(2), 211-218. https://doi.org/10.1242/dev.128793