CD105 protein depletion enhances human adipose-derived stromal cell osteogenesis through reduction of transforming growth factor β1 (TGF-β1) signaling

Benjamin Levi, Derrick C. Wan, Jason P. Glotzbach, Jeong Hyun, Michael Januszyk, Daniel Montoro, Michael Sorkin, Aaron W. James, Emily R. Nelson, Shuli Li, Natalina Quarto, Min Lee, Geoffrey C. Gurtner, Michael T. Longaker

Research output: Contribution to journalArticle

Abstract

Clinically available sources of bone for repair and reconstruction are limited by the accessibility of autologous grafts, infectious risks of cadaveric materials, and durability of synthetic substitutes. Cell-based approaches for skeletal regeneration can potentially fill this need, and adipose tissue represents a promising source for development of such therapies. Here, we enriched for an osteogenic subpopulation of cells derived from human subcutaneous adipose tissue utilizing microfluidicbased single cell transcriptional analysis and fluorescence-activated cell sorting (FACS). Statistical analysis of single cell transcriptional profiles demonstrated that low expression of endoglin (CD105) correlated with a subgroup of adipose-derived cells with increased osteogenic gene expression. FACS-sorted CD105 low cells demonstrated significantly enhanced in vitro osteogenic differentiation and in vivo bone regeneration when compared with either CD105 high or unsorted cells. Evaluation of the endoglin pathway suggested that enhanced osteogenesis among CD105 low adipose-derived cells is likely due to identification of a subpopulation with lower TGF-β1/Smad2 signaling. These findings thus highlight a potential avenue to promote osteogenesis in adipose-derived mesenchymal cells for skeletal regeneration.

Original languageEnglish (US)
Pages (from-to)39497-39509
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number45
DOIs
StatePublished - Nov 11 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Levi, B., Wan, D. C., Glotzbach, J. P., Hyun, J., Januszyk, M., Montoro, D., Sorkin, M., James, A. W., Nelson, E. R., Li, S., Quarto, N., Lee, M., Gurtner, G. C., & Longaker, M. T. (2011). CD105 protein depletion enhances human adipose-derived stromal cell osteogenesis through reduction of transforming growth factor β1 (TGF-β1) signaling. Journal of Biological Chemistry, 286(45), 39497-39509. https://doi.org/10.1074/jbc.M111.256529