Oxygen tension directs chondrogenic differentiation of myelo-monocytic progenitors during endochondral bone formation

Jessica Shafer, Alan R. Davis, Francis H. Gannon, Christine M. Fouletier-Dilling, Zawaunyka Lazard, Kevin Moran, Zbigniew Gugala, Mustafa Ozen, Michael Ittmann, Michael H. Heggeness, Elizabeth Olmsted-Davis

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Synthesis of bone requires both essential progenitors to form the various structures and the correct microenvironment for their differentiation. To identify these factors, we have used a system that exploits bone morphogenetic protein's ability to induce endochondral bone formation rapidly. One of the earliest events observed was the influx and proliferation of fibroblastic cells that express both vascular smooth muscle cell markers, α smooth muscle actin (α SMA), smooth muscle myosin heavy chain, and the monocytic marker CD68. The expression of these factors was lost by days 4 to 5, coincident with the upregulation of Sox9 and the appearance of chondrocytes. Studies with a cyclization recombination (Cre)/lox system, in which a myeloid-specific promoter driving Cre recombinase can irreversibly unblock expression of β-galactosidase only in cells of myeloid origin, showed specific activity in the newly formed chondrocytes. These results suggest that early chondrocyte progenitors are of myeloid origin. Simultaneous with this recruitment, we determined that a numbers of these cells were in a hypoxic state, indicative of a low-oxygen environment. The cells in the hypoxic regions were undergoing chondrogenesis, whereas cells in adjacent normoxic regions appeared to be assembling into new vessels, suggesting that the oxygen microenvironment is critical for establishment of the cartilage.

Original languageEnglish (US)
Pages (from-to)2011-2019
Number of pages9
JournalTissue Engineering
Volume13
Issue number8
DOIs
StatePublished - Aug 2007

Fingerprint

Chondrocytes
Osteogenesis
Muscle
Bone
Cyclization
Oxygen
Genetic Recombination
Galactosidases
Smooth Muscle Myosins
Chondrogenesis
Recombinases
Bone Morphogenetic Proteins
Myosin Heavy Chains
Cartilage
Myeloid Cells
Vascular Smooth Muscle
Smooth Muscle Myocytes
Smooth Muscle
Actins
Up-Regulation

ASJC Scopus subject areas

  • Biophysics
  • Cell Biology
  • Biotechnology

Cite this

Shafer, J., Davis, A. R., Gannon, F. H., Fouletier-Dilling, C. M., Lazard, Z., Moran, K., ... Olmsted-Davis, E. (2007). Oxygen tension directs chondrogenic differentiation of myelo-monocytic progenitors during endochondral bone formation. Tissue Engineering, 13(8), 2011-2019. https://doi.org/10.1089/ten.2006.0063

Oxygen tension directs chondrogenic differentiation of myelo-monocytic progenitors during endochondral bone formation. / Shafer, Jessica; Davis, Alan R.; Gannon, Francis H.; Fouletier-Dilling, Christine M.; Lazard, Zawaunyka; Moran, Kevin; Gugala, Zbigniew; Ozen, Mustafa; Ittmann, Michael; Heggeness, Michael H.; Olmsted-Davis, Elizabeth.

In: Tissue Engineering, Vol. 13, No. 8, 08.2007, p. 2011-2019.

Research output: Contribution to journalArticle

Shafer, J, Davis, AR, Gannon, FH, Fouletier-Dilling, CM, Lazard, Z, Moran, K, Gugala, Z, Ozen, M, Ittmann, M, Heggeness, MH & Olmsted-Davis, E 2007, 'Oxygen tension directs chondrogenic differentiation of myelo-monocytic progenitors during endochondral bone formation', Tissue Engineering, vol. 13, no. 8, pp. 2011-2019. https://doi.org/10.1089/ten.2006.0063
Shafer, Jessica ; Davis, Alan R. ; Gannon, Francis H. ; Fouletier-Dilling, Christine M. ; Lazard, Zawaunyka ; Moran, Kevin ; Gugala, Zbigniew ; Ozen, Mustafa ; Ittmann, Michael ; Heggeness, Michael H. ; Olmsted-Davis, Elizabeth. / Oxygen tension directs chondrogenic differentiation of myelo-monocytic progenitors during endochondral bone formation. In: Tissue Engineering. 2007 ; Vol. 13, No. 8. pp. 2011-2019.
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