Switch from canonical to noncanonical Wnt signaling mediates high glucose-induced adipogenesis

Emily C. Keats, James M. Dominguez, Maria B. Grant, Zia A. Khan

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Human bone marrow mesenchymal progenitor cells (MPCs) are multipotent cells that play an essential role in endogenous repair and the maintenance of the stem cell niche. We have recently shown that high levels of glucose, conditions mimicking diabetes, cause impairment of MPCs, resulting in enhanced adipogenesis and suppression of osteogenesis. This implies that diabetes may lead to reduced endogenous repair mechanisms through altering the differentiation potential of MPCs and, consequently, disrupting the stem cell niche. Phenotypic alterations in the bone marrow of long-term diabetic patients closely resemble this observation. Here, we show that high levels of glucose selectively enhance autogenous Wnt11 expression in MPCs to stimulate adipogenesis through the Wnt/protein kinase C noncanonical pathway. This novel mechanism may account for increased bone marrow adipogenesis, severe bone loss, and reduced vascular stem cells leading to chronic secondary complications of diabetes. Stem Cells 2014;32:1649-1660

Original languageEnglish
Pages (from-to)1649-1660
Number of pages12
JournalStem Cells
Volume32
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Adipogenesis
Mesenchymal Stromal Cells
Stem Cell Niche
Glucose
Bone Marrow
Stem Cells
Wnt Proteins
Diabetes Complications
Osteogenesis
Protein Kinase C
Blood Vessels
Maintenance
Bone and Bones

Keywords

  • Adipogenesis
  • Cell-autogenous regulation
  • Diabetes
  • Noncanonical signaling
  • Protein kinase C
  • Wnt signaling

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine
  • Medicine(all)

Cite this

Switch from canonical to noncanonical Wnt signaling mediates high glucose-induced adipogenesis. / Keats, Emily C.; Dominguez, James M.; Grant, Maria B.; Khan, Zia A.

In: Stem Cells, Vol. 32, No. 6, 2014, p. 1649-1660.

Research output: Contribution to journalArticle

Keats, Emily C. ; Dominguez, James M. ; Grant, Maria B. ; Khan, Zia A. / Switch from canonical to noncanonical Wnt signaling mediates high glucose-induced adipogenesis. In: Stem Cells. 2014 ; Vol. 32, No. 6. pp. 1649-1660.
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