Abstract

Osterix (Osx or Sp7) is a zinc-finger-family transcriptional factor essential for osteoblast differentiation in mammals. The Osx-Cre mouse line (also known as Osx1-GFP::Cre) expresses GFP::Cre fusion protein from a BAC transgene containing the Osx regulatory sequence. The mouse strain was initially characterized during embryogenesis, and found to target mainly osteoblast-lineage cells. Because the strain has been increasingly used in postnatal studies, it is important to evaluate its targeting specificity in mice after birth. By crossing the Osx-Cre mouse with the R26-mT/mG reporter line and analyzing the progenies at two months of age, we find that Osx-Cre targets not only osteoblasts, osteocytes and hypertrophic chondrocytes as expected, but also stromal cells, adipocytes and perivascular cells in the bone marrow. The targeting of adipocytes and perivascular cells appears to be specific to those residing within the bone marrow, as the same cell types elsewhere are not targeted. Beyond the skeleton, Osx-Cre also targets the olfactory glomerular cells, and a subset of the gastric and intestinal epithelium. Thus, potential contributions from the non-osteoblast-lineage cells should be considered when Osx-Cre is used to study gene functions in postnatal mice.

Highlights

  • Osterix (Osx or Sp7) is a zinc finger family transcriptional factor critical for osteoblast differentiation[1]

  • We find that within the skeleton, Osx-Cre targets osteoblast lineage cells and a subset of chondrocytes, and stromal cells, adipocytes and perivascular cells within the bone marrow

  • Osx-Cre and bone marrow mesenchymal stem cells Evidence suggests that mesenchymal stem cells (MSCs) residing within the adult bone marrow produce osteoblasts, adipocytes and bone marrow stromal cells necessary for postnatal tissue homeostasis [17,18]

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Summary

Introduction

Osterix (Osx or Sp7) is a zinc finger family transcriptional factor critical for osteoblast differentiation[1]. In Osx-null embryos, cartilage elements are largely normal but osteoblast differentiation fails to complete, resulting in a complete lack of bone tissue [1]. In these embryos, Runx expression is relatively normal, but other osteoblast markers including Col1a1, Bsp, and osteocalcin are either absent or severely suppressed [1]. Osx functions genetically downstream of Runx to control osteoblast differentiation[6]. In addition to its role in embryonic osteoblast differentiation, Osx plays a critical role in the formation and function of postnatal osteoblast and osteocyte [7]

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