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

Keats EC, Dominguez JM, Grant MB, Khan ZA
Source: Stem Cells
Publication Date: (2014)
Issue: 32(6): 1649-60
Research Area:
Stem Cells
Basic Research
Cells used in publication:
Mesenchymal stem cell (MSC), human
Species: human
Tissue Origin: bone marrow
Bone Marrow, Human, Unprocessed
Species: human
Tissue Origin: bone marrow
Mononuclear, bone marrow, human
Species: human
Tissue Origin: bone marrow
Culture Media:
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.