Bone morphogenetic protein 2 promotes osteogenesis of bone marrow stromal cells in type 2 diabetic rats via the Wnt signaling pathway |
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| Institution: | 1. Chair of Orthopedics, Department of Orthopedics, Jena University Hospital, Waldkrankenhaus “Rudolf Elle,” Klosterlausnitzer Str 81, D-07607 Eisenberg, Germany;2. Experimental Rheumatology Unit, Department of Orthopedics, Jena University Hospital, Waldkrankenhaus “Rudolf Elle”, Klosterlausnitzer Str 81, D-07607 Eisenberg, Germany;3. Chair of Materials Science, Otto Schott Institute of Materials Research, Friedrich Schiller University Jena, Löbdergraben 32, D-07743 Jena, Germany;4. Jena School for Microbial Communication (JSMC), Friedrich Schiller University Jena, Neugasse 23, D-07743 Jena, Germany;5. Institute of Laboratory Animal Sciences and Welfare, Jena University Hospital, Dornburger Str. 23, D-07743 Jena, Germany;6. BAM Bundesanstalt für Materialforschung und – prüfung (BAM), Unter den Eichen 87, D-12205 Berlin, Germany;7. Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Humboldstr. 10, D-07743 Jena, Germany |
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| Abstract: | Type 2 diabetes mellitus impairs osteogenesis in bone marrow stromal cells (BMSCs). Bone morphogenetic protein 2 (BMP2) has been extensively applied for bone defect restoration and has been shown to activate the Wnt signaling pathway. The objective of this study was to investigate the effects of BMP2 on the cell proliferation and osteogenesis of type 2 diabetic BMSCs in rats and explore whether BMP2 induced osteogenesis via the stimulation of Wnt signaling pathway. The cell experiments were divided into DM (diabetic BMSCs), BMP25 (induced with 25 ng/ml BMP2), BMP100 (induced with 100 ng/ml BMP2) and BMP25 + XAV groups. All cells with or without the different concentrations of BMP2 were cultured under the same experimental conditions. The in vitro results indicated that BMP2 enhanced cell proliferation by 130%–157% and osteogenic differentiation by approximately two-fold in type 2 diabetic BMSCs. The expression levels of β-catenin, cyclin D1, Runx2 and c-myc related to the Wnt signaling pathway were also upregulated from 180% to 212% in BMP2-induced type 2 diabetic rat BMSCs, while the level of GSK3β decreased to 43%. In BMP2-induced type 2 diabetic BMSCs with calcium phosphate cement (CPC) scaffolds for osteoblast study in vivo, the appearance of newly formed bone dramatically increased to 175% compared with type 2 diabetic BMSCs. These data demonstrated that BMP2 enhanced bone regeneration in diabetic BMSCs by stimulating the Wnt signaling pathway with the accumulation of β-catenin and the depressed expression of GSK3β. Diabetic BMSCs associated with BMP2 might be a potential tissue-engineered construct for bone defects in type 2 diabetes mellitus. |
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| Keywords: | BMP2 Type 2 diabetic BMSCs Osteogenesis Wnt signaling pathway |
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