Abstract
Bone regeneration disorders are a significant problem in patients with type 2 diabetes mellitus. Bone marrow stromal cells (BMSCs) are recognized as ideal seed cells for tissue engineering because they can stimulate osteogenesis during bone regeneration. Therefore, the aim of this study was to investigate the osteogenic potential of BMSCs derived from type 2 diabetic rats and the pathogenic characteristics of dysfunctional BMSCs that affect osteogenesis. BMSCs were isolated from normal and high-fat diet+streptozotocin-induced type 2 diabetic rats. Cell metabolic activity, alkaline phosphatase (ALP) activity, mineralization and osteogenic gene expression were reduced in the type 2 diabetic rat BMSCs. The expression levels of Wnt signaling genes, such as β-catenin, cyclin D1 and c-myc, were also significantly decreased in the type 2 diabetic rat BMSCs, but the expression of GSK3β remained unchanged. The derived BMSCs were cultured on calcium phosphate cement (CPC) scaffolds and placed subcutaneously into nude mice for eight weeks; they were detected at a low level in newly formed bone. The osteogenic potential of the type 2 diabetic rat BMSCs was not impaired by the culture environment, but it was impaired by inhibition of the Wnt signaling pathway, likely due to an insufficient accumulation of β-catenin rather than because of GSK3β stimulation. Using BMSCs derived from diabetic subjects could offer an alternative method of regenerating bone together with the use of supplementary growth factors to stimulate the Wnt signaling pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaline Phosphatase / genetics
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Alkaline Phosphatase / metabolism
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Animals
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / metabolism*
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Bone Marrow Cells / pathology
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Calcium Phosphates / chemistry
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Diabetes Mellitus, Experimental / chemically induced
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Diabetes Mellitus, Experimental / genetics
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Diabetes Mellitus, Experimental / metabolism*
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Diabetes Mellitus, Experimental / pathology
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Diabetes Mellitus, Type 2 / genetics
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Diabetes Mellitus, Type 2 / metabolism
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Diabetes Mellitus, Type 2 / pathology
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Diet, High-Fat / adverse effects
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Gene Expression Regulation
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Glycogen Synthase Kinase 3 / genetics
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Male
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Mesenchymal Stem Cell Transplantation
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Mesenchymal Stem Cells / drug effects
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Mesenchymal Stem Cells / metabolism*
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Mesenchymal Stem Cells / pathology
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Mice
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Mice, Nude
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Osteogenesis / genetics*
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Primary Cell Culture
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism
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Rats
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Rats, Sprague-Dawley
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Streptozocin
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Transplantation, Heterologous
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Wnt Signaling Pathway
Substances
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Calcium Phosphates
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Ccnd1 protein, rat
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Proto-Oncogene Proteins c-myc
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Cyclin D1
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Streptozocin
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calcium phosphate
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, mouse
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Gsk3b protein, rat
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Glycogen Synthase Kinase 3
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Alkaline Phosphatase
Grants and funding
This work was supported by Shanghai Leading Academic Discipline Project (Project Number: S30206), Science and Technology committee of Shanghai (08DZ2271100 and ZZjdyx13107), Shanghai Leading Academic Discipline Project (T0202), and National Natural Science Funds of China (81300912 and 81201201). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.