Osteoblast Precursors, but Not Mature Osteoblasts, Move into Developing and Fractured Bones along with Invading Blood Vessels

By C. Maes, Tatsuya Kobayashi, M. Selig, S. Torrekens, Sanford I. Roth, S. Mackem, G. Carmeliet, H. Kronenberg. Developmental Cell, 2010

900 citations recorded by the source corpus.

SUMMARY During endochondral bone development, the first osteoblasts differentiate in the perichondrium surrounding avascular cartilaginous rudiments; the source of trabecular osteoblasts inside the later bone is, however, unknown. Here, we generated tamoxifen-inducible transgenic mice bred to Rosa26R-LacZ reporter mice to follow the fates of stage-selective subsets of osteoblast lineage cells. Pulse-chase studies showed that osterix-expressing osteoblast precursors, labeled in the perichondrium prior to vascular invasion of the cartilage, give rise to trabecular osteoblasts, osteocytes, and stromal cells inside the developing bone. Throughout the translocation, some precursors were found to intimately associate with invading blood vessels, in pericyte-like fashion. A similar coinvasion occurs during endochondral healing of bone fractures. In contrast, perichondrial mature osteoblasts did not exhibit perivascular localization and remained in the outer cortex of developing bones. These findings reveal the specific involvement of immature osteoblast precursors in the coupled vascular and osteogenic transformation essential to endochondral bone development and repair.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/327da34682554e31c4dd45fb2f46384b54eecbfc

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. H. Kronenberg
2. G. Genové
3. C. Betsholtz
4. A. Armulik
5. Berislav Zlokovic
6. D. Hanahan

In Molecular Biology

1. Fanxin Long
2. D. Ornitz
3. H. Kronenberg
4. A. Armulik
5. G. Genové
6. B. Olsen
7. T. Partridge
8. Kai Hu

In Oncology

1. Fanxin Long
2. B. Olsen
3. Kai Hu
4. D. Scadden
5. C. Iadecola

Citations in the corpus

• Leptin Receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow (2014, neutral): “During fetal development, Osterix (Osx) is expressed by cells that form bone marrow stroma, including perivascular, osteo- genic, and adipogenic cells (Liu et al., 2013; Maes et al., 2010).”
• Building strong bones: molecular regulation of the osteoblast lineage (2011, background): “In addition, the invading blood vessels seem to provide a vehicle for the perichondrial cells (which express OSX and are considered to be preosteoblasts in this Review) to enter the nascent bone marrow, where they differentiate into osteoblast”
• An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration (2011, background): “Embryonic expression of Pax7 (Jostes et al., 1990; Lepper and Fan, 2010; Mansouri et al., 1996) predicts possible expression of this gene in the adult CNS as well as in craniofacial structures developed from cephalic neural crest cells.”
• Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. (2011, background): “During the healing of bone fractures, the invading vasculature was shown to be closely associated with osteoblasts (Maes et al., 2010).”
• Development of the endochondral skeleton. (2013, background): “center to generate the trabecular bone (Maes et al. 2010).”
• The roles of vascular endothelial growth factor in bone repair and regeneration (2016, background): “VEGF functions not only as one of the most important regulators of vascular development and angiogenesis [6, 7], it also plays critical roles in skeletal development [8-10].”
• Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation (2014, background): “Blood vessels then invade through the bone collar into the hypertrophic cartilage, bringing in osteoblast progenitors from the perichondrium (2), which lay down bone matrix to form the primary ossification center (POC); the cartilage matrix is degraded; and the proximal and distal growth plates, com”
• Endogenous Bone Marrow MSCs Are Dynamic, Fate-Restricted Participants in Bone Maintenance and Regeneration (2012, methodology): “Some studies indicate that bone-surface osteoblasts are postmitotic and replaced by unspecified immature cells (Kalajzic et al., 2008; McCulloch and Heersche, 1988; Owen and MacPherson, 1963), while in development, osteoblasts divide (Dominici et al., 2009; Maes et al., 2010).”