Switch from Canonical to Noncanonical Wnt Signaling Mediates High Glucose-Induced Adipogenesis. (23rd May 2014)

• Record Type: Journal Article
• Authors: Keats, Emily C.; Dominguez, James M.; Grant, Maria B.; Khan, Zia A.
• Is Part Of: Stem cells. Volume 32:Number 6(2014:Jun.)
• Page Start: 1649
• Page End: 1660
• Publication Date: 2014-05-23
• Subjects: Adipogenesis -- Diabetes -- Wnt signaling -- Protein kinase C -- Noncanonical signaling -- Cell-autogenous regulation; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1659
• Languages: English
• ISSNs: 1066-5099

Abstract

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