Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells

Wuchen Yang, Dayong Guo, Marie A. Harris, Yong Cui, Jelica Gluhak-Heinrich, Junjie Wu, Xiao Dong Chen, Charles Skinner, Jeffry S. Nyman, James R. Edwards, R. R. Mundy Gregory, Alex Lichtler, Barbara E. Kream, David W. Rowe, Ivo Kalajzic, Val David, Darryl L. Quarles, Demetri Villareal, Greg Scott, Manas RayS. Liu, F. F. Martin James, Yuji Mishina, Stephen E. Harris

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKOob) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKOob mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in a reduced bone formation rate and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKOob osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSCs), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Expression of several MSC marker genes (α-SMA, CD146 and Angiopoietin-1) in vivo, in vitro CFU assays and deletion of Bmp2 in vitro in α-SMAob+ MSCs support our conclusions. Critical roles of Bmp2 in osteoblasts and MSCs are a vital link between bone formation, vascularization and mesenchymal stem cells.

Original languageEnglish (US)
Pages (from-to)4085-4098
Number of pages14
JournalJournal of cell science
Volume126
Issue number18
DOIs
StatePublished - 2013

Keywords

  • Angiogenesis
  • Bmp2
  • Mesenchymal stem cells
  • Osteoblasts
  • VegfA
  • α-SMA+ cells

ASJC Scopus subject areas

  • Cell Biology

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    Yang, W., Guo, D., Harris, M. A., Cui, Y., Gluhak-Heinrich, J., Wu, J., Chen, X. D., Skinner, C., Nyman, J. S., Edwards, J. R., Mundy Gregory, R. R., Lichtler, A., Kream, B. E., Rowe, D. W., Kalajzic, I., David, V., Quarles, D. L., Villareal, D., Scott, G., ... Harris, S. E. (2013). Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells. Journal of cell science, 126(18), 4085-4098. https://doi.org/10.1242/jcs.118596