Open AccessSwitch from Canonical to Noncanonical Wnt Signaling Mediates High Glucose‐Induced Adipogenesis
Author(s) -
Keats Emily C.,
Dominguez James M.,
Grant Maria B.,
Khan Zia A.
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1659
Subject(s) - adipogenesis , biology , wnt signaling pathway , progenitor cell , mesenchymal stem cell , microbiology and biotechnology , stem cell , bone marrow , cellular differentiation , multipotent stem cell , endocrinology , cancer research , signal transduction , immunology , genetics , gene
A bstract 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. S tem C ells 2014;32:1649–1660