Keats Emily C, Dominguez James M, Grant Maria B, Khan Zia A
Department of Pathology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.
Stem Cells. 2014 Jun;32(6):1649-60. doi: 10.1002/stem.1659.
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.
人骨髓间充质祖细胞（MPCs）是多能细胞，在内源性修复和干细胞微环境的维持中起重要作用。我们最近发现，高糖（模拟糖尿病的条件）会导致MPCs功能受损，从而增强脂肪生成并抑制骨生成。这意味着糖尿病可能通过改变MPCs的分化潜能，进而破坏干细胞微环境，导致内源性修复机制减弱。长期糖尿病患者骨髓中的表型改变与这一观察结果非常相似。在这里，我们表明高糖水平选择性地增强MPCs中自分泌Wnt11的表达，通过Wnt/蛋白激酶C非经典途径刺激脂肪生成。这种新机制可能解释了糖尿病患者骨髓脂肪生成增加、严重骨质流失以及血管干细胞减少导致的慢性继发性并发症。
