Bone morphogenetic protein 2 promotes osteogenesis of bone marrow stromal cells in type 2 diabetic rats via the Wnt signaling pathway

被引:25
作者
Qian, Chao [1 ]
Zhu, Chenyuan [1 ]
Yu, Weiqiang [1 ]
Jiang, Xinquan [1 ]
Zhang, Fuqiang [1 ]
Sun, Jain [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Sch Stomatol,Peoples Hosp 9, Dept Prosthodont,Shanghai Key Lab Stomatol, 639 Zhi Zao Ju Rd, Shanghai 200011, Peoples R China
关键词
BMP2; Type 2 diabetic BMSCs; Osteogenesis; Wnt signaling pathway; MESENCHYMAL STEM-CELLS; TITANIUM IMPLANT; GENE-EXPRESSION; MAXILLARY SINUS; SILK SCAFFOLDS; GROWTH-FACTOR; BETA-CATENIN; REGENERATION; INSULIN; DIFFERENTIATION;
D O I
10.1016/j.biocel.2016.09.025
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta-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 GSK3 beta 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 P-catenin and the depressed expression of GSK3 beta. Diabetic BMSCs associated with BMP2 might be a potential tissue-engineered construct for bone defects in type 2 diabetes mellitus. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:143 / 153
页数:11
相关论文
共 61 条
[1]   XAV939: From a Small Inhibitor to a Potent Drug Bioconjugate When Delivered by Gold Nanoparticles [J].
Afifi, Marwa M. ;
Austin, Lauren A. ;
Mackey, Megan A. ;
El-Sayed, Mostafa A. .
BIOCONJUGATE CHEMISTRY, 2014, 25 (02) :207-215
[2]   Inhibition of Id1 Augments Insulin Secretion and Protects Against High-Fat Diet-Induced Glucose Intolerance [J].
Akerfeldt, Mia C. ;
Laybutt, D. Ross .
DIABETES, 2011, 60 (10) :2506-2514
[3]  
[Anonymous], 2014, Biomed Res. Int
[4]   Tissue-Engineered Cartilage: The Crossroads of Biomaterials, Cells and Stimulating Factors [J].
Bhardwaj, Nandana ;
Devi, Dipali ;
Mandal, Biman B. .
MACROMOLECULAR BIOSCIENCE, 2015, 15 (02) :153-182
[5]   Crosstalk between tyrosine kinase receptors, GSK3 and BMP2 signaling during osteoblastic differentiation of human mesenchymal stem cells [J].
Biver, Emmanuel ;
Thouverey, Cyril ;
Magne, David ;
Caverzasio, Joseph .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2014, 382 (01) :120-130
[6]   Bone regeneration using photocrosslinked hydrogel incorporating rhBMP-2 loaded 2-N, 6-O-sulfated chitosan nanoparticles [J].
Cao, Lingyan ;
Werkmeister, Jerome A. ;
Wang, Jing ;
Glattauer, Veronica ;
McLean, Keith M. ;
Liu, Changsheng .
BIOMATERIALS, 2014, 35 (09) :2730-2742
[7]   β-catenin signaling pathway is crucial for bone morphogenetic protein 2 to induce new bone formation [J].
Chen, Yan ;
Whetstone, Heather C. ;
Youn, Andrew ;
Nadesan, Puviindran ;
Chow, Edwin C. Y. ;
Lin, Alvin C. ;
Alman, Benjamin A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (01) :526-533
[8]   Wnt Pathway, an Essential Role in Bone Regeneration [J].
Chen, Yan ;
Alman, Benjamin A. .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2009, 106 (03) :353-362
[9]   Repair of alveolar clefts with recombinant human bone morphogenetic protein (rhBMP-2) in patients with clefts [J].
Chin, M ;
Ng, T ;
Tom, WK ;
Carstens, M .
JOURNAL OF CRANIOFACIAL SURGERY, 2005, 16 (05) :778-789
[10]   Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism [J].
Daniele, Giuseppe ;
Winnier, Deidre ;
Mari, Andrea ;
Bruder, Jan ;
Fourcaudot, Marcel ;
Zuo Pengou ;
Tripathy, Devjit ;
Jenkinson, Christopher ;
Folli, Franco .
DIABETES CARE, 2015, 38 (08) :1509-1517